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Rosie 个案显示 AI 能显著压缩个体化肿瘤治疗流程,但疗效叙事被严重过度包装

这篇文章最有价值的结论不是“AI 做出了抗癌奇迹”,而是“AI 把原本属于研究机构的复杂工作流压缩到了个人可发起的程度”,但作者把一个联合治疗的 n=1 宠物案例包装成平台级突破,科学归因并不成立。
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2026-03-28 原文链接 ↗
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核心观点

  • AI的真实贡献在“编排”不在“神创” 文中最站得住脚的部分,是 ChatGPT、Gemini、Grok 帮作者完成了学习、管线设计、工具排错、伦理文书和治疗排期,这说明大模型已经能把个人的认知与协调能力拉到“准机构级”;但它并没有替代测序、生产、给药和临床判断,真正的硬核执行仍然高度依赖顶级实验室与专家网络。
  • 疗效归因现在根本站不住 Rosie 接受的是手术、TKI、PD-1 抑制剂、个体化 mRNA 疫苗的联合治疗,且观察期只有数月、没有对照组、样本量只有一只狗,所以任何“疫苗起决定性作用”或“AI设计方案有效”的强结论都属于过度归因;尤其在肿瘤学里,多变量混杂足以让个案故事失真。
  • 流程跑通不等于商业能规模化 作者确实跑通了一条“个人发起—高校协作—伦理绕行—定制生产—临床给药”的路径,这证明技术上不是完全不可做;但这条路径依赖极强的人脉、时间投入、机构善意和特批审批,离稳定、低成本、标准化交付差得很远,把它直接上升为可规模化业务,明显跳步了。
  • 肿瘤异质性是被轻描淡写的硬问题 文中已经出现“有的肿瘤缩小、有的肿瘤继续长且基因特征不同”的情况,这恰恰说明个体化癌症疫苗最大的难点不是做出一个构建体,而是面对同一患者体内不同克隆的分化与逃逸;这不是小插曲,而是未来疗效和产品化的核心障碍。
  • 这是一篇半技术复盘、半创业路演 文章前半段靠真实技术细节建立可信度,后半段迅速转向“为什么不能让更多人用上”“我们相信可以规模化”,这不是中立记录,而是明显带有 PR 和项目预热色彩;判断上应把它当成“高质量创始人叙事”,而不是“临床证据发布”。

跟我们的关联

  • 对 ATou 意味着什么 这说明顶级 AI 使用方式不是“问答案”,而是把模型当跨学科项目经理、研究助理和合规 copilot;下一步可以把这种能力抽象成一套“复杂任务工作流模板”,用于科研、医疗、法务、投融资等高摩擦领域。
  • 对 Neta 意味着什么 这再次验证了 AI 最大的商业机会常常不是发明新能力,而是把已存在的专业能力变得可达、可理解、可执行;下一步应重点看 access layer、workflow layer、compliance layer,而不是只盯基础模型。
  • 对 Uota 意味着什么 这是一个典型的“叙事极强但证据未闭环”的案例,讨论时不能被技术细节和情感张力带着走;下一步可以围绕“什么叫流程验证、什么叫疗效验证、什么叫商业验证”拆成三层来辩。
  • 对 ATou/Neta/Uota 都意味着什么 这篇材料适合当作“AI 放大个体能力边界”的正反教材:正面是 AI 确实提升了行动效率,反面是个案叙事极易滑向因果夸张;下一步可据此建立一套评估 AI 创业故事的检查清单。

讨论引子

1. 如果把 Rosie 案例里的 mRNA 疫苗拿掉,只保留 TKI 和 PD-1,疗效会差多少,作者现在有没有任何证据能回答这个问题? 2. 一条依赖顶尖高校、特殊审批和创始人超强执行力的路径,怎样才算真正具备“规模化”资格? 3. AI 在这类高风险场景里最该被定义成“认知放大器”“研究编排器”还是“科学共创者”,边界该怎么划?

大家都问我怎么做到的。就在这里**

第 1 部分:Rosie 的故事**

2023 年 6 月: 大约三年前,发现 Rosie 有些不对劲。她头部和腿上长了肿块,明显让她很难受。接下来的 11 个月里,我带她看了三次兽医。每次就诊,兽医都很敷衍,没有给出任何癌症诊断。

2024 年 5 月: 到这时,肿胀已经非常严重,并开始出血。我坚持让兽医认真处理。Rosie 做了手术,切除了肿胀的肿块,并取了活检。癌症终于被确诊。晚了整整 11 个月。

致命的预后把选择摆在面前:接受它,或者倾尽所有去对抗。为了弄懂癌症以及能做什么,我用 ChatGPT 疯狂查资料、啃资料。同时还在做一份全职工作:经营一家 AI 咨询公司。

确诊后、以及早期做完研究后,我和一位新的兽医讨论了下一步。Rosie 起初接受的是:

  • 化疗:非常昂贵。

  • 标准自体免疫疗法:效果不佳。

2024 年 7 月: 为了寻找更好的治疗选择,在走投无路中,我选了一家高端兽医诊所。效果很好,很多大块肿物通过手术被切除。还剩下一块很大的肿物,需要截肢才能切掉。我反复权衡,最后决定不截。

这家诊所很不错,但后续治疗负担不起。听朋友推荐,我找到了同样是兽医的 Mina Ghaly 医生。

2024 年 8 月: Ghaly 医生是这段故事里被忽视的英雄之一。他是唯一真正愿意接纳我这个所谓“公民科学家”的兽医。这位新兽医在促成后续许多事情上至关重要。差不多也是在这个时候,我对癌症药物研发的理解之旅才刚开始。我知道 AlphaFold 因为能加速靶向癌症疗法的发现而备受吹捧,我想看看这是否适用于 Rosie 的情况。我继续深问 ChatGPT,它建议第一步是对 Rosie 的 DNA 以及癌细胞的 DNA 做基因组测序。

2024 年 9 月–2025 年 1 月: 癌症仍在毫无阻碍地扩散,必须换一套新的治疗方案。ChatGPT o1 指出了新南威尔士大学(UNSW)的 Martin Smith 教授是基因组测序的负责人。

这里使用的基因组测序,并不是像 23andMe 那种用口腔拭子做部分测序。它是完整的全基因组测序,需要对组织以及提取出来的 DNA 进行特定方式的保存。我亲自把组织样本从兽医那里开车送到 Garvan Institute。Garvan Institute 的 Pavel Bitter 团队在为测序提取 DNA 方面发挥了关键作用。随后 DNA 由快递送到 UNSW 的 Ramaciotti Centre,由 Martin Smith 教授完成测序工作——这是关键的深度科学步骤。就在几十年前,这一步可能要花超过十亿美元,如今成本在迅速下降,同时速度也变得越来越快。

https://www.ccralliance.org/about

2025 年 2 月–5 月: 拿到原始 DNA 数据后,数据分析真正开始了。为了形成一套数据转换流程,我们同时使用了 Gemini、Grok 和 ChatGPT。我和团队最终在 c-KIT 基因里找到一个突变,这是肥大细胞癌的已知驱动因素。我们用 AlphaFold 2 对 Rosie 的突变 c-KIT 蛋白进行建模和理解——而在 9 年前,这一步还需要晶体学等专门的实验技术。

2025 年 6 月–7 月: 目标是用一种配体去关闭 c-KIT 突变,从而阻止癌症的失控生长。既然已经锁定了一个潜在的致癌突变,我们就有两条路径可以考虑:

但首先,什么是配体?→ 任何能够特异性结合更大的“靶”分子(通常是蛋白质)以实现某种目的的分子

(A) 使用遗传算法——一种数值优化技术——来发现一种全新的配体。我们整合了更多脚本和模拟引擎,开发出一个在模拟中有效的候选配体。从培养皿到小鼠模型,再到犬只,可能需要几年。进一步权衡后,全新配体的风险与审批流程让这条路在 Rosie 的时间窗口内不可行。但这个配体候选仍然存在——如果审批环境哪天跟上了,它或许还有机会。

(B) 对一个包含 100 万以上既有配体的库做对接,寻找匹配项。跑了两周、筛了 100 万个候选后——尤里卡——找到了匹配!那一刻感觉终于抓住了可能奏效的东西,但这条路很快也开始瓦解。匹配到的是一种已有专利的化合物,这意味着使用或合成它会面临巨大的法律障碍。

不过,我还是联系上了专利持有人,尝试在他们现有法律路径之外申请同情用药豁免。可以理解,这对他们来说风险太高,他们拒绝了。

这是一段极其低谷的时刻。走到这里,已经做了太多:测了健康与癌变 DNA,用最前沿的工具开发治疗候选,识别了已知化合物。感觉像是把可能的空间都走遍了,还是没戏,仿佛命中注定如此。

2025 年 8 月: 在花了两周优先陪 Rosie 好好相处后,一个念头冒出来:如果能自己做一支疫苗呢?那一晚我和 ChatGPT 反复辩论各种可能,最后落在看起来最值得下注的一条路上:肽类新抗原疫苗。

疫苗思路与配体对接是根本性的转向:与其只是阻断推动癌症生长的蛋白,疫苗让免疫系统重新识别并主动清除癌细胞。

我给 UNSW 的 Ramaciotti Institute 的 Martin Smith 教授发了邮件,他把我介绍给 Deborah Burnett 博士。Burnett 博士说,她虽然没有肽类新抗原疫苗的经验,但有 mRNA 疫苗的经验。这又是一个关键例子:人类与聊天机器人之间来回弹跳的构想,对整个过程至关重要。按照 Burnett 博士的建议,我回到 ChatGPT,得到确认:mRNA 路线会更快。

两条管线同时启动:

  • mRNA 疫苗构建体开发

  • mRNA 疫苗伦理审批

2025 年 9 月–10 月中旬:

疫苗开发:

大约 9 月初,一个快速生长的肿瘤需要切除。这给了我们一个提取并测序 RNA 的机会。

又来一遍:组织冰上保存,Garvan Institute 的 Pavel Bitter 团队,RNA 快递到 UNSW,由 UNSW 的 Ramaciotti Centre 里 Martin 教授团队完成测序。

回到数据分析,我们把范围缩小到 7 个在 mRNA 与 DNA 中都高度普遍的表位。这个交集就是“冒烟的枪”。因为 mRNA 表达反映的是细胞实际产生的蛋白,这 7 个靶点代表了最有希望触发强免疫反应的候选。

为了让你体会一下我当时的处境,可以试着让你最喜欢的 LLM 聊天机器人列出 7 个随机表位。仅作示例,我从 Gemini 得到的 7 个随机表位如下:

另外,我只是把上面列出的表位丢给 Gemini,让它生成一个疫苗构建体,它就给了我下面这个。注意,这个构建体并不唯一,会取决于要优化什么:

PADRE—GPGPG—WITQCFLPVFLAQP—GPGPG—GVGSPYVSRLLGICL—AAY—KVAELVHFL—AAY—FLWGPRALV—AAY—SLLMWITQC—AAY—KIFGSLAFL

也可以用你偏好的聊天机器人自己生成一个疫苗构建体试试!

在 Rosie 的特定案例里,我用 Gemini 2 Pro 来架构多表位疫苗构建体,加入经过优化的连接肽与佐剂。得到的序列随后通过 Grok 3 进行二次启发式精修,以确保结构稳定,并尽量降低连接位点的免疫原性。

免责声明:上面列出的疫苗构建体仅用于教育目的,不建议用于药物研发或任何治疗方案的一部分。

伦理审批(2025 年 9 月–10 月中旬):

穿过伦理审批流程等同于第二份全职工作。除了本职工作之外,还要再投入 120 小时的材料与文书。为了扛住负担,我再次求助聊天机器人,做了一次巨大的战术转向。我用它们来解码那些细微的法律术语与晦涩的监管语言,以获得试验许可。

新南威尔士大学能开发疫苗,但没有针对这种“n=1”试验的流程。要新建流程会拖到 2026 年中。Rosie 没时间。

到这一步,我的努力已经被认为很不寻常。UNSW 和一些本地媒体在 2025 年 7 月报道过(当然没有全球范围的轰动)。但有些专家一直在关注。我引起了美国 Canine Cancer Alliance 的 Mari Maeda 博士的注意——她可以说是全球犬类癌症领域最权威的人物之一。

Maeda 博士把我介绍给昆士兰大学的 Rachel Allavena 教授。Allavena 教授手上已有兼容的试验审批。通过 Google meet 听到消息时,我装作很淡定,只是庆幸试验能推进。挂断后真实反应是疯狂握拳庆祝,差点把 Rosie 的雷雨恐惧都激出来。

2025 年 10 月–11 月: 试验文件完成后,UNSW 的 Pall Thordarson 教授及其团队终于可以开始生产疫苗。经过他们 6 周的专业工作,疫苗准备好了。

2025 年 12 月: 关键时刻到了。Rosie 跳上车,我们一路向北。我们开了 10 小时车到昆士兰开始治疗。但我当时并不知道,相关校区还要从布里斯班再开 4 小时才能到。

终于到了昆士兰大学兽医科学学院,我们准备继续:

  • 一支专门设计的 mRNA 疫苗——精准制导的武器,用来打击癌症。它的研发管线由 ChatGPT o1 设计,候选开发由 Gemini Pro 2 落地实现,最终设计由 Grok 3 Thinking 验证。

  • 用于削弱癌症防御的辅助药物——没有这些,mRNA 疫苗基本会被弹开,或者在真正打到癌症之前就失效。

2026 年 1 月: 三周后,癌变区域肿胀起来——其实是好迹象。假性进展。这意味着 T 细胞正在蜂拥而上。

六周后,有两处癌变区域在缩小。

2026 年 2 月: 这两处区域,尤其是 Rosie 的腿周围,正在回到看起来正常的状态。还残留一些平坦的小鼓包,推测是已经死亡的癌细胞留下的痕迹,也就是瘢痕组织。

尽管 Rosie 腿上的肿瘤在缩小,她屁股后方仍有一个肿块在增长。这个肿块被手术切除,并再次送去做基因组分析。

2026 年 3 月: 3 月 8 日,来自那颗无反应肿瘤的数据到了,分析开始。

3 月 10 日,早期迹象显示,无反应的癌症与疫苗所针对的那种癌症存在差异。

3 月 11 日,故事在澳大利亚曝光。

3 月 12 日,故事点燃了 X。

过去一周像一场旋风。三年前,我看到 Rosie 需要帮助。我尽了一切可能。幸运的是,我有机器学习背景,也赢得了世界级专家的信任,他们认为这件事值得追下去。

如果没有 AI 聊天机器人,这些事情不可能以这样的速度发生。

第 2 部分:AI 的故事

先回应一下关于 AI 到底做了什么的争论。

这不是把 DNA 上传到 ChatGPT,然后提示它:请做一支零失误的疫苗。

这花了几个月,需要 ChatGPT、Gemini 和 Grok——在不同阶段做不同的事情。

AI 做的最难的工作,也就是核心科学:把原始基因组数据变成一份疫苗处方。

我们一开始有大约 300GB 的原始测序数据——Rosie 肿瘤的全基因组测序数据,以及一份匹配的正常血样,后来还加上肿瘤的 RNA 测序。最终输出大概只有半页:一个编码 7 个新抗原靶点的 mRNA 疫苗构建体。

作为非生物学背景的人,我依赖聊天机器人来帮我设计一条生物信息学管线,也大量依赖聊天机器人去实现它。

下面这些是给想弄懂流程的人看的具体工具。对大多数读者来说,这个列表可能只会带来更多问题而不是答案。我花了几个月才把它们弄明白,而且那时我已经做这件事一年多了。那么不再赘述,关键组件如下:

  • 用 BWA-MEM 做比对

  • 用 GATK Mutect2(一种贝叶斯体细胞模型)做变异检测

  • 用 Ensembl VEP 做注释

  • 用 pVACseq + NetMHCpan-4.1——一个神经网络,用来预测突变肽是否会与 Rosie 的特定免疫分子(DLA 等位基因)结合

我后来理解到,这些属于人类精准肿瘤学管线里同一类工具。

之后我们用 RNA 测序数据去验证 DNA 预测出的靶点,确认这些突变确实在肿瘤里被表达。只有 RNA 表达得到确认的表位被保留下来。这些表位最终成为我送到实验室合成的疫苗构建体。

这些工具的实现与使用,可能就是各研究机构里研究生和博士后工作的主要内容。我不认为每个人都该掌握我掌握的东西,才能使用这些工具。我认为它本来不必这么复杂。

那聊天机器人到底做了什么?

它们不可或缺——但方式和很多人想的不一样。

  • 规划与管线设计: 用 ChatGPT 和 Gemini 把整个生物信息学工作流画出来——用哪些工具、按什么顺序、输入输出分别是什么。

  • 排错: 工具失败时(而且几乎一直在失败——依赖冲突、参考基因组不兼容、注释格式不匹配),我们用聊天机器人一起调试。犬基因组的注释程度远不如人类基因组,很多工具默认面对的是人类数据。每一步都阻力重重。

  • 候选筛选与构建体设计: Grok 帮我们筛选表位候选,后来还帮助把最终确认的靶点转成 mRNA 疫苗构建体——也就是带连接肽、UTR、并针对犬细胞做了密码子优化的真实序列。

  • 治疗方案设计: ChatGPT 和 Gemini 帮我们设计多模态方案——推演药物相互作用、时间安排、免疫协同,以及不同疗法的分阶段推进。这涉及在药理学、肿瘤免疫学与兽医肿瘤学之间持续数周的迭代分析。

  • 教育: 我不是生物学家。聊天机器人教我从分子层面理解癌症,理解新抗原是什么,MHC/DLA 分子做什么,主干突变与分支突变的区别是什么,肿瘤微环境是什么,以及这些为什么重要。

  • 伦理、合规与协调: 聊天机器人帮助我撰写大约 100 页的伦理审批文件,理解澳大利亚各州的监管环境,并与多所大学协调推进。

疫苗不是单独使用的。

聊天机器人还帮助设计了一整套多模态治疗方案——不只是疫苗,还有围绕疫苗的完整免疫策略:

  • 个体化 mRNA 新抗原疫苗——编码 7 个靶点,用来训练 Rosie 的 T 细胞识别并杀死她特定的癌细胞

  • 酪氨酸激酶抑制剂(TKI)——靶向 Rosie 的 c-KIT 突变,提供基础抗肿瘤压力,并调节肿瘤微环境

  • PD-1 免疫检查点抑制剂——解除 Rosie 的 T 细胞刹车,让它们对癌症释放全部杀伤潜力

我看到很多网上评论说,真正起作用的只是 PD-1 抑制剂,或者只是酪氨酸激酶抑制剂。这误解了癌症的真实运作方式。肿瘤不是坐在那里等着被杀——它会主动构建一个抑制性的微环境,腐化周围免疫细胞,生长自己的血供,并躲避免疫系统。

如果这是《星际迷航》,癌症的肿瘤微环境就是飞船的护盾。你可以发射再多光子鱼雷——由 mRNA 训练出来的 T 细胞——只要护盾还在,就什么都打不进去。

没有任何单一疗法能独自打穿癌症的护盾。TKI 和 PD-1 抑制剂从不同角度把护盾放下来。

TKI 针对的是肿瘤的供给基础设施。癌症需要血管来供养自己,并会主动生长新的血管——这个过程叫血管生成。TKI 阻断它,使肿瘤缺乏营养与氧气。它也会直接抑制驱动癌症生长信号的 c-KIT 突变。用《星际迷航》的说法,它是在瘫痪敌方引擎、切断生命维持系统的供电。

PD-1 抑制剂解决的是另一个问题。癌细胞会在表面展示一种蛋白,向靠近的、被 mRNA 训练过的 T 细胞发出“退下”的信号——等于告诉免疫系统的士兵把武器收起来。PD-1 抑制剂阻断这个信号,让 T 细胞不再被欺骗而退缩。如果说 TKI 是从外部把护盾放下来,PD-1 抑制剂就是从内部关掉它——切断肿瘤对那些被派来摧毁它的细胞的隐身能力。

两者一起上阵:TKI 与 PD-1——护盾放下,mRNA 训练的 T 细胞光子鱼雷就能穿透。

这些疗法的顺序与时间安排极其重要——不能把免疫抑制治疗、TKI 与 PD-1,和免疫激活的 mRNA 疫苗同时给。ChatGPT 和 Gemini 帮我梳理药理相互作用、减量计划,以及跨越数周、反复推演的分阶段推进方案。

聊天机器人没有做的事:

它们没有采样。没有分离或测序 DNA。没有实体生产疫苗。没有给药。每一步都需要许多杰出科学家——包括在 UNSW mRNA Institute 生产疫苗的 Pall Thordarson 教授;在昆士兰大学给药的 Rachel Allavena 教授与 José Granados 博士;以及在整个生物信息学过程中提供专业指导的 Martin Smith 教授。

总结:

聊天机器人让一个个体拥有了研究机构级别的行动力——规划、学习、排错、合规,以及把基因组数据转成疫苗处方、并设计围绕它的治疗方案这类真正的科学设计工作。但每一步都与人类并肩完成。正是这种组合,让它成为可能。

https://www.abc.net.au/listen/programs/healthreport/dog-owner-ai-cancer-treatment/105462166

第 3 部分:下一步是什么

自从 Rosie 确诊以来,我竭尽所能去帮助她。但这件事引发的反应——涌来的支持、以及成千上万来自焦急狗主人的信息——让一件事变得清晰。

Rosie 接受的是一个完全个体化、多模态的 mRNA 癌症方案。一只狗,一支疫苗,从零开始设计。治疗三个月后,她表现出强烈的好转迹象。

那是容易的部分。

反复萦绕的念头是:为什么要痴迷到这种程度,才能走到这里?有太多不必要的障碍。太多技术与工具,本可以更容易获取。科学已经存在。AI 已经存在。缺口在于让它触手可及。

这些年,我一直和朋友讨论该做一家什么样的 AI 公司。大约三个月前,其中一个朋友说——你为什么还要问这个问题?显然是帮助更多人做到你为 Rosie 做到的事。当时我并不信服。我做了很多,确实有了更多可尝试的选项,但并没有突破。现在,治疗三个月后,Rosie 在改善。而社区的回应也压倒性地强烈。

现在才是难的部分。

过去一周,我一直在和所有参与者沟通,想弄清楚这个流程到底能不能更规模化。

我们相信可以。

这将是下一章。它从一只狗开始,但不会止于一只。

很快会分享更多。

Best,

Paul

Everyone asks me how I did it. Here it is**

大家都问我怎么做到的。就在这里**

Part 1: Rosie's Story**

第 1 部分:Rosie 的故事**

June 2023: About three years ago, I noticed something wrong with Rosie. She had swollen lumps on her head and leg, and it was noticeably bothering her. Over the course of the next 11 months I took her to a veterinarian three times. During each visit, the vet was dismissive and no cancer diagnosis was made.

2023 年 6 月: 大约三年前,发现 Rosie 有些不对劲。她头部和腿上长了肿块,明显让她很难受。接下来的 11 个月里,我带她看了三次兽医。每次就诊,兽医都很敷衍,没有给出任何癌症诊断。

May 2024: At this point, the swelling had become severe and started bleeding. I insisted that the vet address it. Rosie had surgery to remove the swollen masses and a biopsy was taken. This is when the cancer was finally diagnosed. Eleven months late.

2024 年 5 月: 到这时,肿胀已经非常严重,并开始出血。我坚持让兽医认真处理。Rosie 做了手术,切除了肿胀的肿块,并取了活检。癌症终于被确诊。晚了整整 11 个月。

The fatal prognosis left me with a choice: accept it, or throw everything I had at it. I used ChatGPT and devoured everything I could to understand cancer and what I could do about it. All the while continuing a full-time job: running an AI consulting business.

致命的预后把选择摆在面前:接受它,或者倾尽所有去对抗。为了弄懂癌症以及能做什么,我用 ChatGPT 疯狂查资料、啃资料。同时还在做一份全职工作:经营一家 AI 咨询公司。

After the diagnosis and my early research, I discussed what to do with a new veterinarian. Rosie was initially put on:

确诊后、以及早期做完研究后,我和一位新的兽医讨论了下一步。Rosie 起初接受的是:

  • Chemotherapy - very expensive.
  • 化疗:非常昂贵。
  • Standard autologous immunotherapy - not effective.
  • 标准自体免疫疗法:效果不佳。

July 2024: Desperate for better treatment options, I settled on a high-end veterinarian clinic. With great success, many large masses were removed by surgery. One large mass remained - it would have required amputation of the leg. I debated but decided against it.

2024 年 7 月: 为了寻找更好的治疗选择,在走投无路中,我选了一家高端兽医诊所。效果很好,很多大块肿物通过手术被切除。还剩下一块很大的肿物,需要截肢才能切掉。我反复权衡,最后决定不截。

The clinic was great but on-going treatment was unaffordable. On a friend’s recommendation, I arrived at Dr. Mina Ghaly, also a vet.

这家诊所很不错,但后续治疗负担不起。听朋友推荐,我找到了同样是兽医的 Mina Ghaly 医生。

August 2024: Dr. Ghaly is one of the unsung heroes of this story. He was the only vet that was truly receptive to me - a "citizen scientist." This new vet was critical in facilitating much of what was to come. About this time my journey in understanding cancer drug development had just begun. I knew that AlphaFold had been touted for its ability to accelerate the discovery of targeted cancer therapies and I wanted to see if that was applicable to Rosie’s case. I queried ChatGPT deeper on this, and the first step it suggested was to get genomic sequencing of Rosie’s DNA and her cancer cells’ DNA.

2024 年 8 月: Ghaly 医生是这段故事里被忽视的英雄之一。他是唯一真正愿意接纳我这个所谓“公民科学家”的兽医。这位新兽医在促成后续许多事情上至关重要。差不多也是在这个时候,我对癌症药物研发的理解之旅才刚开始。我知道 AlphaFold 因为能加速靶向癌症疗法的发现而备受吹捧,我想看看这是否适用于 Rosie 的情况。我继续深问 ChatGPT,它建议第一步是对 Rosie 的 DNA 以及癌细胞的 DNA 做基因组测序。

September 2024–January 2025: With cancer continuing to spread unabated, a new therapeutic regimen was needed. ChatGPT o1 identified Professor Martin Smith at the University of New South Wales (UNSW) as the lead for genomic sequencing.

2024 年 9 月–2025 年 1 月: 癌症仍在毫无阻碍地扩散,必须换一套新的治疗方案。ChatGPT o1 指出了新南威尔士大学(UNSW)的 Martin Smith 教授是基因组测序的负责人。

Using tissue that was collected in January, genomic sequencing employed here was not like a cheek swab with partial sequencing from 23andMe. This was a full and complete genome sequence and required specific preservation of the tissue and extracted DNA. I drove the tissue samples from the vet to the Garvan Institute myself. Pavel Bitter's team at the Garvan Institute played a critical role in extracting DNA for sequencing. The DNA was then couriered to UNSW's Ramaciotti Centre for Professor Martin Smith to do his sequencing work - one of the critical deep science steps that just a couple of decades ago would have cost over a billion dollars and is rapidly coming down in price, while getting much, much faster.

这里使用的基因组测序,并不是像 23andMe 那种用口腔拭子做部分测序。它是完整的全基因组测序,需要对组织以及提取出来的 DNA 进行特定方式的保存。我亲自把组织样本从兽医那里开车送到 Garvan Institute。Garvan Institute 的 Pavel Bitter 团队在为测序提取 DNA 方面发挥了关键作用。随后 DNA 由快递送到 UNSW 的 Ramaciotti Centre,由 Martin Smith 教授完成测序工作——这是关键的深度科学步骤。就在几十年前,这一步可能要花超过十亿美元,如今成本在迅速下降,同时速度也变得越来越快。

February–May 2025: With the raw DNA data in hand, data analysis began in earnest. Gemini, Grok, and ChatGPT were all used in arriving at a data transformation protocol. My team and I eventually found a mutation in the c-KIT gene, a known driver of mast cell cancer. AlphaFold 2 was used to model and understand Rosie’s mutated c-KIT protein - a step that would have required specialised experimental techniques like crystallography only 9 years ago.

2025 年 2 月–5 月: 拿到原始 DNA 数据后,数据分析真正开始了。为了形成一套数据转换流程,我们同时使用了 Gemini、Grok 和 ChatGPT。我和团队最终在 c-KIT 基因里找到一个突变,这是肥大细胞癌的已知驱动因素。我们用 AlphaFold 2 对 Rosie 的突变 c-KIT 蛋白进行建模和理解——而在 9 年前,这一步还需要晶体学等专门的实验技术。

June–July 2025: The goal was to use a ligand to switch off the c-KIT mutation and hence stop the unfettered cancer growth. With a prospective cancerous mutation identified, we now had two pathways to consider:

2025 年 6 月–7 月: 目标是用一种配体去关闭 c-KIT 突变,从而阻止癌症的失控生长。既然已经锁定了一个潜在的致癌突变,我们就有两条路径可以考虑:

But first, what is a ligand ? → Any molecule that binds specifically to a larger "target" molecule (usually a protein) to serve a purpose

但首先,什么是配体?→ 任何能够特异性结合更大的“靶”分子(通常是蛋白质)以实现某种目的的分子

(A) Using genetic algorithms - a numerical optimisation technique - to discover a novel ligand. Pulling together more scripts and simulation engines, we developed a candidate that worked in simulation. It could have taken years to go from petri dishes, to mouse models and finally to dogs. After further consideration, the risks and approvals process for a novel ligand made this approach unworkable within Rosie's timeframe. But the ligand candidate still exists - and if the approvals landscape ever catches up, it may yet have its day.

(A) 使用遗传算法——一种数值优化技术——来发现一种全新的配体。我们整合了更多脚本和模拟引擎,开发出一个在模拟中有效的候选配体。从培养皿到小鼠模型,再到犬只,可能需要几年。进一步权衡后,全新配体的风险与审批流程让这条路在 Rosie 的时间窗口内不可行。但这个配体候选仍然存在——如果审批环境哪天跟上了,它或许还有机会。

(B) Docking a library of pre-existing 1M+ ligands to look for a match. After two weeks of running 1 million candidates - eureka - a match! It felt like we finally had something that could work, but then this pathway began to unravel as well. The match was for an existing patented compound. This meant that there were huge legal barriers to use or synthesise the compound.

(B) 对一个包含 100 万以上既有配体的库做对接,寻找匹配项。跑了两周、筛了 100 万个候选后——尤里卡——找到了匹配!那一刻感觉终于抓住了可能奏效的东西,但这条路很快也开始瓦解。匹配到的是一种已有专利的化合物,这意味着使用或合成它会面临巨大的法律障碍。

I did however make contact with the patent holder and seek a compassionate use exemption outside their existing legal pathways. Understandably this was too high a risk for them to consider and they declined.

不过,我还是联系上了专利持有人,尝试在他们现有法律路径之外申请同情用药豁免。可以理解,这对他们来说风险太高,他们拒绝了。

This was a major low point. We had come so far - sequencing the healthy and cancerous DNA, running state-of-the-art tooling to develop candidates for treatment, identifying known compounds. It really felt like we had exhausted the space and it just was not meant to be.

这是一段极其低谷的时刻。走到这里,已经做了太多:测了健康与癌变 DNA,用最前沿的工具开发治疗候选,识别了已知化合物。感觉像是把可能的空间都走遍了,还是没戏,仿佛命中注定如此。

August 2025: After two weeks of prioritising quality time with Rosie, an idea came to me - “what if it was possible to create a vaccine myself?” I spent the night with ChatGPT debating possibilities. Eventually we arrived at what looked like the best bet: a peptide neoantigen vaccine.

2025 年 8 月: 在花了两周优先陪 Rosie 好好相处后,一个念头冒出来:如果能自己做一支疫苗呢?那一晚我和 ChatGPT 反复辩论各种可能,最后落在看起来最值得下注的一条路上:肽类新抗原疫苗。

The vaccine approach is a fundamental shift from ligand docking; rather than merely obstructing the proteins that fuel cancer growth, vaccines enable the immune system to re-identify and actively eliminate cancerous cells.

疫苗思路与配体对接是根本性的转向:与其只是阻断推动癌症生长的蛋白,疫苗让免疫系统重新识别并主动清除癌细胞。

I emailed Professor Martin Smith at UNSW's Ramaciotti Institute and he referred me to Dr. Deborah Burnett. Dr. Burnett said that while she did not have experience in peptide neoantigen vaccines, she did have experience with mRNA vaccines. This is yet another example of the ideation bouncing between humans and chat bots that was critical to the process. Following this advice from Dr. Burnett, I reverted back to ChatGPT and got confirmation that the mRNA approach would be faster.

我给 UNSW 的 Ramaciotti Institute 的 Martin Smith 教授发了邮件,他把我介绍给 Deborah Burnett 博士。Burnett 博士说,她虽然没有肽类新抗原疫苗的经验,但有 mRNA 疫苗的经验。这又是一个关键例子:人类与聊天机器人之间来回弹跳的构想,对整个过程至关重要。按照 Burnett 博士的建议,我回到 ChatGPT,得到确认:mRNA 路线会更快。

Two pipelines were initiated in parallel:

两条管线同时启动:

  • mRNA vaccine construct development
  • mRNA 疫苗构建体开发
  • mRNA vaccine ethics approval
  • mRNA 疫苗伦理审批

September–mid October 2025:

2025 年 9 月–10 月中旬:

Vaccine development:

疫苗开发:

Around early September, a fast-growing tumour needed to be removed. This was an opportunity for RNA extraction and sequencing.

大约 9 月初,一个快速生长的肿瘤需要切除。这给了我们一个提取并测序 RNA 的机会。

Here we go again: tissue on ice, Pavel Bitter's team at the Garvan Institute, RNA couriered to UNSW, sequencing by Professor Martin's team at UNSW's Ramaciotti Centre.

又来一遍:组织冰上保存,Garvan Institute 的 Pavel Bitter 团队,RNA 快递到 UNSW,由 UNSW 的 Ramaciotti Centre 里 Martin 教授团队完成测序。

Returning to the data analysis, we narrowed the field to 7 epitopes highly prevalent in both the mRNA and DNA. This intersection was the “smoking gun.” Because mRNA expression reveals the cell’s actual protein production, these 7 targets represent the most viable candidates for triggering a robust immune response.

回到数据分析,我们把范围缩小到 7 个在 mRNA 与 DNA 中都高度普遍的表位。这个交集就是“冒烟的枪”。因为 mRNA 表达反映的是细胞实际产生的蛋白,这 7 个靶点代表了最有希望触发强免疫反应的候选。

To give you a flavour of being in my shoes, try asking your favourite LLM chat bot to list 7 random epitopes. For illustration purposes only, here are 7 random epitopes I got from Gemini:

为了让你体会一下我当时的处境,可以试着让你最喜欢的 LLM 聊天机器人列出 7 个随机表位。仅作示例,我从 Gemini 得到的 7 个随机表位如下:

And, here is one vaccine construct that I got from Gemini by merely passing the epitopes listed above and asking it to create one. Note that the construct is not unique, and depends on what one is optimising for:

另外,我只是把上面列出的表位丢给 Gemini,让它生成一个疫苗构建体,它就给了我下面这个。注意,这个构建体并不唯一,会取决于要优化什么:

PADRE—GPGPG—WITQCFLPVFLAQP—GPGPG—GVGSPYVSRLLGICL—AAY—KVAELVHFL—AAY—FLWGPRALV—AAY—SLLMWITQC—AAY—KIFGSLAFL

PADRE—GPGPG—WITQCFLPVFLAQP—GPGPG—GVGSPYVSRLLGICL—AAY—KVAELVHFL—AAY—FLWGPRALV—AAY—SLLMWITQC—AAY—KIFGSLAFL

Try creating your own vaccine construct using your preferred chat bot of choice !

也可以用你偏好的聊天机器人自己生成一个疫苗构建体试试!

For the Rosie-specific case, I utilised Gemini 2 Pro to architect the multi-epitope vaccine construct, incorporating optimised linkers and adjuvants. The resulting sequence was then subjected to a secondary heuristic refinement via Grok 3, ensuring structural stability and minimising junctional immunogenicity.

在 Rosie 的特定案例里,我用 Gemini 2 Pro 来架构多表位疫苗构建体,加入经过优化的连接肽与佐剂。得到的序列随后通过 Grok 3 进行二次启发式精修,以确保结构稳定,并尽量降低连接位点的免疫原性。

DISCLAIMER: The vaccine construct listed above is strictly for educational purposes and is not indicated to be used for the purposes of drug development or as part of any treatment protocols.

免责声明:上面列出的疫苗构建体仅用于教育目的,不建议用于药物研发或任何治疗方案的一部分。

Ethics approval (September–mid October 2025):

伦理审批(2025 年 9 月–10 月中旬):

Navigating the ethics approval process was a second full-time job, demanding 120 hours of paperwork alongside my actual career. To manage the load, I turned back to chat bots for a massive tactical shift. I used them to decode the subtle legalese and opaque regulatory language necessary to secure permission for the trial.

穿过伦理审批流程等同于第二份全职工作。除了本职工作之外,还要再投入 120 小时的材料与文书。为了扛住负担,我再次求助聊天机器人,做了一次巨大的战术转向。我用它们来解码那些细微的法律术语与晦涩的监管语言,以获得试验许可。

The University of New South Wales was able to develop the vaccine but did not have a process for a trial of this "n=1" kind. To create a new process would have taken until mid-2026. Rosie did not have time.

新南威尔士大学能开发疫苗,但没有针对这种“n=1”试验的流程。要新建流程会拖到 2026 年中。Rosie 没时间。

My efforts to this point had already been considered unusual. UNSW and some other local media published them in July 2025 (albeit without the global fanfare). However, some experts were watching. I had managed to get the attention of Dr. Mari Maeda of the Canine Cancer Alliance in the USA - arguably the world's foremost authority on canine cancer.

到这一步,我的努力已经被认为很不寻常。UNSW 和一些本地媒体在 2025 年 7 月报道过(当然没有全球范围的轰动)。但有些专家一直在关注。我引起了美国 Canine Cancer Alliance 的 Mari Maeda 博士的注意——她可以说是全球犬类癌症领域最权威的人物之一。

Dr. Maeda connected me with Professor Rachel Allavena at the University of Queensland. Professor Allavena had an existing compatible trial approval. On hearing the news over a Google meet, I acted nonchalantly - glad the trial could go ahead. My real reaction after the call, was fist pumping so hard Rosie's fear of thunder was almost provoked.

Maeda 博士把我介绍给昆士兰大学的 Rachel Allavena 教授。Allavena 教授手上已有兼容的试验审批。通过 Google meet 听到消息时,我装作很淡定,只是庆幸试验能推进。挂断后真实反应是疯狂握拳庆祝,差点把 Rosie 的雷雨恐惧都激出来。

October–November 2025: With the trial paperwork completed, Professor Pall Thordarson and his team at UNSW could now commence manufacturing the vaccine. After 6 weeks of their expert work, the vaccine was ready.

2025 年 10 月–11 月: 试验文件完成后,UNSW 的 Pall Thordarson 教授及其团队终于可以开始生产疫苗。经过他们 6 周的专业工作,疫苗准备好了。

December 2025: Go time. Rosie jumped into the car and we headed north. We took the 10-hour drive to Queensland to commence treatment. However, unbeknownst to me, the relevant campus was another four hours' drive out of Brisbane.

2025 年 12 月: 关键时刻到了。Rosie 跳上车,我们一路向北。我们开了 10 小时车到昆士兰开始治疗。但我当时并不知道,相关校区还要从布里斯班再开 4 小时才能到。

Finally at the University of Queensland’s School of Veterinary Science, we were ready to proceed:

终于到了昆士兰大学兽医科学学院,我们准备继续:

  • A specifically designed mRNA vaccine - a precision-guided weapon to strike the cancer, developed with a pipeline designed by ChatGPT o1, implemented for candidate development by Gemini Pro 2, and with the final design validated by Grok 3 Thinking.
  • 一支专门设计的 mRNA 疫苗——精准制导的武器,用来打击癌症。它的研发管线由 ChatGPT o1 设计,候选开发由 Gemini Pro 2 落地实现,最终设计由 Grok 3 Thinking 验证。
  • Supporting drugs to weaken the cancer's defences - without these, mRNA vaccines effectively just bounce off or are rendered useless before they can hit the cancer.
  • 用于削弱癌症防御的辅助药物——没有这些,mRNA 疫苗基本会被弹开,或者在真正打到癌症之前就失效。

January 2026: Three weeks in, the cancerous areas swelled up - actually a good sign. Pseudoprogression. It means the T-cells are swarming.

2026 年 1 月: 三周后,癌变区域肿胀起来——其实是好迹象。假性进展。这意味着 T 细胞正在蜂拥而上。

Six weeks in, two cancerous areas were shrinking.

六周后,有两处癌变区域在缩小。

February 2026: The two areas, specifically around Rosie's legs, were returning to what appeared normal. Residual flat bumps from now presumably dead cancer cells remained, i.e., scar tissue.

2026 年 2 月: 这两处区域,尤其是 Rosie 的腿周围,正在回到看起来正常的状态。还残留一些平坦的小鼓包,推测是已经死亡的癌细胞留下的痕迹,也就是瘢痕组织。

Despite the tumors on Rosie’s legs receding in size, there was still a growing mass on Rosie's rear. This mass was surgically removed and sent again for genomic analysis.

尽管 Rosie 腿上的肿瘤在缩小,她屁股后方仍有一个肿块在增长。这个肿块被手术切除,并再次送去做基因组分析。

March 2026: March 8th - the data from the non-responsive tumour arrived, analysis commenced.

2026 年 3 月: 3 月 8 日,来自那颗无反应肿瘤的数据到了,分析开始。

March 10th - early signs suggested there were differences in the non-responsive cancer compared to the one the vaccine was designed for.

3 月 10 日,早期迹象显示,无反应的癌症与疫苗所针对的那种癌症存在差异。

March 11th - the story broke in Australia.

3 月 11 日,故事在澳大利亚曝光。

March 12th - the story ignited X.

3 月 12 日,故事点燃了 X。

The last week has been a whirlwind. Three years ago I saw that Rosie needed help. I did everything I could. I was fortunate to have a background in machine learning and win the trust of world leading experts who saw something worth pursuing.

过去一周像一场旋风。三年前,我看到 Rosie 需要帮助。我尽了一切可能。幸运的是,我有机器学习背景,也赢得了世界级专家的信任,他们认为这件事值得追下去。

The pace at which these events transpired could not have been possible without AI chat bots.

如果没有 AI 聊天机器人,这些事情不可能以这样的速度发生。

Part 2: The AI Story

第 2 部分:AI 的故事

Let me address the debate about what AI actually did.

先回应一下关于 AI 到底做了什么的争论。

This was not an upload of DNA to ChatGPT with the prompt: "Please make a vaccine with no mistakes."

这不是把 DNA 上传到 ChatGPT,然后提示它:请做一支零失误的疫苗。

It took months. It required ChatGPT, Gemini, and Grok - each for different things at different stages.

这花了几个月,需要 ChatGPT、Gemini 和 Grok——在不同阶段做不同的事情。

The hardest work done by AI - the core science: turning raw genomic data into a vaccine prescription.

AI 做的最难的工作,也就是核心科学:把原始基因组数据变成一份疫苗处方。

We started with ~300 gigabytes of raw sequencing data - whole genome sequencing of Rosie's tumour and a matched normal blood sample, plus later RNA sequencing of the tumour. The final output was roughly half a page: an mRNA vaccine construct encoding 7 neoantigen targets.

我们一开始有大约 300GB 的原始测序数据——Rosie 肿瘤的全基因组测序数据,以及一份匹配的正常血样,后来还加上肿瘤的 RNA 测序。最终输出大概只有半页:一个编码 7 个新抗原靶点的 mRNA 疫苗构建体。

As a non-biologist, I relied on chat bots to help me design a bioinformatics pipeline. I also worked with chat bots extensively to implement it.

作为非生物学背景的人,我依赖聊天机器人来帮我设计一条生物信息学管线,也大量依赖聊天机器人去实现它。

These are the specific tools for people wanting to understand the process. For most readers this list will probably raise more questions than answers. It took me months to wrap my head around them, and I had the benefit of working on this for over a year at that point. So without further ado, the critical components:

下面这些是给想弄懂流程的人看的具体工具。对大多数读者来说,这个列表可能只会带来更多问题而不是答案。我花了几个月才把它们弄明白,而且那时我已经做这件事一年多了。那么不再赘述,关键组件如下:

  • BWA-MEM for alignment
  • 用 BWA-MEM 做比对
  • GATK Mutect2 (a Bayesian somatic model) for variant calling
  • 用 GATK Mutect2(一种贝叶斯体细胞模型)做变异检测
  • Ensembl VEP for annotation
  • 用 Ensembl VEP 做注释
  • pVACseq with NetMHCpan-4.1 - a neural network that predicts whether a mutant peptide will bind to Rosie's specific immune molecules (DLA alleles)
  • 用 pVACseq + NetMHCpan-4.1——一个神经网络,用来预测突变肽是否会与 Rosie 的特定免疫分子(DLA 等位基因)结合

What I have come to understand is that these are the same class of tools used in human precision oncology pipelines.

我后来理解到,这些属于人类精准肿瘤学管线里同一类工具。

We then validated the DNA-predicted targets against RNA sequencing data to confirm the mutations were actually being expressed by the tumour. Only epitopes with confirmed RNA expression were retained. These epitopes became the vaccine construct that I sent to the lab for synthesis.

之后我们用 RNA 测序数据去验证 DNA 预测出的靶点,确认这些突变确实在肿瘤里被表达。只有 RNA 表达得到确认的表位被保留下来。这些表位最终成为我送到实验室合成的疫苗构建体。

The implementation and use of these tools are probably the substance of graduate and postdoc activity in various institutes. I do not think everyone should have to know what I know to be able to use these tools. I think this was far more complex than it needed to be.

这些工具的实现与使用,可能就是各研究机构里研究生和博士后工作的主要内容。我不认为每个人都该掌握我掌握的东西,才能使用这些工具。我认为它本来不必这么复杂。

So what did the chat bots actually do?

那聊天机器人到底做了什么?

They were indispensable - but not in the way people assume.

它们不可或缺——但方式和很多人想的不一样。

  • Planning & pipeline design: I used ChatGPT and Gemini to map out the entire bioinformatics workflow - what tools to use, in what order, what the inputs and outputs should be.
  • 规划与管线设计: 用 ChatGPT 和 Gemini 把整个生物信息学工作流画出来——用哪些工具、按什么顺序、输入输出分别是什么。
  • Troubleshooting: When tools failed (and they failed constantly - dependency conflicts, reference genome incompatibilities, annotation format mismatches), we used chat bots to debug. The dog genome is far less well-annotated than the human genome, and many tools assume human data. Every step had friction.
  • 排错: 工具失败时(而且几乎一直在失败——依赖冲突、参考基因组不兼容、注释格式不匹配),我们用聊天机器人一起调试。犬基因组的注释程度远不如人类基因组,很多工具默认面对的是人类数据。每一步都阻力重重。
  • Candidate filtering & construct design: Grok helped filter our epitope candidates and later helped convert the final confirmed targets into the mRNA vaccine construct - the actual sequence with linkers, UTRs, and codon optimisation for canine cells.
  • 候选筛选与构建体设计: Grok 帮我们筛选表位候选,后来还帮助把最终确认的靶点转成 mRNA 疫苗构建体——也就是带连接肽、UTR、并针对犬细胞做了密码子优化的真实序列。
  • Treatment protocol design: ChatGPT and Gemini helped design the multimodal protocol - working through drug interactions, timing, immunological synergies, and the phased rollout of distinct therapies. This involved weeks of iterative analysis across pharmacology, tumour immunology, and veterinary oncology.
  • 治疗方案设计: ChatGPT 和 Gemini 帮我们设计多模态方案——推演药物相互作用、时间安排、免疫协同,以及不同疗法的分阶段推进。这涉及在药理学、肿瘤免疫学与兽医肿瘤学之间持续数周的迭代分析。
  • Education: I am not a biologist. The chat bots taught me what cancer is at a molecular level, what neoantigens are, what MHC/DLA molecules do, what truncal vs branch mutations mean, what the tumour microenvironment is, and why any of this matters.
  • 教育: 我不是生物学家。聊天机器人教我从分子层面理解癌症,理解新抗原是什么,MHC/DLA 分子做什么,主干突变与分支突变的区别是什么,肿瘤微环境是什么,以及这些为什么重要。
  • Ethics, compliance & coordination: The chat bots helped me write the ~100 pages of ethics approval documents, navigate the regulatory landscape across Australian states, and coordinate with multiple universities.
  • 伦理、合规与协调: 聊天机器人帮助我撰写大约 100 页的伦理审批文件,理解澳大利亚各州的监管环境,并与多所大学协调推进。

The vaccine was not given alone.

疫苗不是单独使用的。

The chat bots also helped design a multimodal treatment protocol - not just the vaccine, but the entire immunological strategy around it:

聊天机器人还帮助设计了一整套多模态治疗方案——不只是疫苗,还有围绕疫苗的完整免疫策略:

  • A personalised mRNA neoantigen vaccine - encoding 7 targets designed to train Rosie's T-cells to recognise and kill her specific cancer cells
  • 个体化 mRNA 新抗原疫苗——编码 7 个靶点,用来训练 Rosie 的 T 细胞识别并杀死她特定的癌细胞
  • A tyrosine kinase inhibitor - targeting Rosie's c-KIT mutation, providing foundational anti-tumour pressure and modulating the tumour microenvironment
  • 酪氨酸激酶抑制剂(TKI)——靶向 Rosie 的 c-KIT 突变,提供基础抗肿瘤压力,并调节肿瘤微环境
  • A PD-1 checkpoint inhibitor - removing the brakes from Rosie's T-cells, unleashing their full killing potential against the cancer
  • PD-1 免疫检查点抑制剂——解除 Rosie 的 T 细胞刹车,让它们对癌症释放全部杀伤潜力

I have seen a lot of commentary online suggesting it was really just the PD-1 inhibitor doing the heavy lifting, or just the tyrosine kinase inhibitor. This misunderstands how cancer actually works. A tumour does not just sit there waiting to be killed - it actively builds a suppressive microenvironment around itself, corrupting nearby immune cells, growing its own blood supply, and hiding from the immune system.

我看到很多网上评论说,真正起作用的只是 PD-1 抑制剂,或者只是酪氨酸激酶抑制剂。这误解了癌症的真实运作方式。肿瘤不是坐在那里等着被杀——它会主动构建一个抑制性的微环境,腐化周围免疫细胞,生长自己的血供,并躲避免疫系统。

If this were Star Trek, the cancer tumour microenvironment is the ship's shields. You can fire as many photon torpedoes - mRNA trained T cells - as you want. If the shields are up, nothing gets through.

如果这是《星际迷航》,癌症的肿瘤微环境就是飞船的护盾。你可以发射再多光子鱼雷——由 mRNA 训练出来的 T 细胞——只要护盾还在,就什么都打不进去。

No single therapy punches through cancer’s “shields” alone. The tyrosine kinase inhibitor and the PD-1 inhibitor take the shields down - but from different angles.

没有任何单一疗法能独自打穿癌症的护盾。TKI 和 PD-1 抑制剂从不同角度把护盾放下来。

The TKI targets the tumour's supply infrastructure. Cancer needs blood vessels to feed itself and it actively grows new ones - a process called angiogenesis. The TKI blocks this, starving the tumour of nutrients and oxygen. It also directly inhibits the c-KIT mutation driving the cancer's growth signal. In Star Trek terms, it is disabling the enemy's engines and cutting power to life support.

TKI 针对的是肿瘤的供给基础设施。癌症需要血管来供养自己,并会主动生长新的血管——这个过程叫血管生成。TKI 阻断它,使肿瘤缺乏营养与氧气。它也会直接抑制驱动癌症生长信号的 c-KIT 突变。用《星际迷航》的说法,它是在瘫痪敌方引擎、切断生命维持系统的供电。

The PD-1 inhibitor works on a different problem entirely. Cancer cells display a protein on their surface that sends a "stand down" signal to any mRNA trained T-cell that approaches - essentially telling the immune system's soldiers to holster their weapons. The PD-1 inhibitor blocks that signal, so the T-cells can no longer be fooled into backing off. If the TKI is taking down the shields from the outside, the PD-1 inhibitor is disabling them from within - shutting down the tumour's ability to cloak itself from the very cells sent to destroy it.

PD-1 抑制剂解决的是另一个问题。癌细胞会在表面展示一种蛋白,向靠近的、被 mRNA 训练过的 T 细胞发出“退下”的信号——等于告诉免疫系统的士兵把武器收起来。PD-1 抑制剂阻断这个信号,让 T 细胞不再被欺骗而退缩。如果说 TKI 是从外部把护盾放下来,PD-1 抑制剂就是从内部关掉它——切断肿瘤对那些被派来摧毁它的细胞的隐身能力。

Firing these two together: the TKI & PD-1 - the shields come down and the mRNA trained T-cell photon torpedoes get through.

两者一起上阵:TKI 与 PD-1——护盾放下,mRNA 训练的 T 细胞光子鱼雷就能穿透。

The sequencing and timing of these therapies mattered enormously - you can not give immunosuppressant treatments, TKI’s & PD-1’s alongside an immune-activating mRNA vaccine. ChatGPT and Gemini helped me work through the pharmacological interactions, tapering schedules, and phased rollout across weeks of back-and-forth.

这些疗法的顺序与时间安排极其重要——不能把免疫抑制治疗、TKI 与 PD-1,和免疫激活的 mRNA 疫苗同时给。ChatGPT 和 Gemini 帮我梳理药理相互作用、减量计划,以及跨越数周、反复推演的分阶段推进方案。

What the chat bots did NOT do:

聊天机器人没有做的事:

They did not collect samples. They did not isolate or sequence the DNA. They did not physically manufacture the vaccine. They did not administer it. Many brilliant scientists were required - including Professor Pall Thordarson at the UNSW mRNA Institute who manufactured the vaccine, Professor Rachel Allavena & Dr. José Granados at the University of Queensland who administered it, and Professor Martin Smith who provided expert guidance on the bioinformatics throughout.

它们没有采样。没有分离或测序 DNA。没有实体生产疫苗。没有给药。每一步都需要许多杰出科学家——包括在 UNSW mRNA Institute 生产疫苗的 Pall Thordarson 教授;在昆士兰大学给药的 Rachel Allavena 教授与 José Granados 博士;以及在整个生物信息学过程中提供专业指导的 Martin Smith 教授。

In summary:

总结:

The chat bots empowered me as an individual to act with the power of a research institute - planning, education, troubleshooting, compliance, and yes, real scientific design work in converting genomic data to a vaccine prescription and designing the treatment protocol around it. But they worked alongside humans at every step. The combination is what made it possible.

聊天机器人让一个个体拥有了研究机构级别的行动力——规划、学习、排错、合规,以及把基因组数据转成疫苗处方、并设计围绕它的治疗方案这类真正的科学设计工作。但每一步都与人类并肩完成。正是这种组合,让它成为可能。

Part 3: What is next

第 3 部分:下一步是什么

Since Rosie's diagnosis, I have done everything I can to help her. But the reaction to this story - the outpouring of support, the thousands of messages from people with dogs in distress - has made something clear.

自从 Rosie 确诊以来,我竭尽所能去帮助她。但这件事引发的反应——涌来的支持、以及成千上万来自焦急狗主人的信息——让一件事变得清晰。

Rosie received a fully individualised, multimodal mRNA cancer protocol. One dog, one vaccine, designed from scratch. Three months in, she is showing strong signs of improvement.

Rosie 接受的是一个完全个体化、多模态的 mRNA 癌症方案。一只狗,一支疫苗,从零开始设计。治疗三个月后,她表现出强烈的好转迹象。

That was the easy part.

那是容易的部分。

What I keep coming back to is this: I do not know why I had to be this obsessed to get here. There are so many unnecessary barriers. So many techniques and tools that could be made far easier to access. The science exists. The AI exists. The gap is in making it reachable.

反复萦绕的念头是:为什么要痴迷到这种程度,才能走到这里?有太多不必要的障碍。太多技术与工具,本可以更容易获取。科学已经存在。AI 已经存在。缺口在于让它触手可及。

For years, I have discussed with friends what kind of AI company I should start. About 3 months ago, one of them said - "why are you even asking that question? Surely it is helping other people do what you did for Rosie." At the time, I was not convinced. I had done a lot, and it had given me more options to try, but there had been no breakthrough. Now, three months into treatment, Rosie is improving. And the response from the community has been overwhelming.

这些年,我一直和朋友讨论该做一家什么样的 AI 公司。大约三个月前,其中一个朋友说——你为什么还要问这个问题?显然是帮助更多人做到你为 Rosie 做到的事。当时我并不信服。我做了很多,确实有了更多可尝试的选项,但并没有突破。现在,治疗三个月后,Rosie 在改善。而社区的回应也压倒性地强烈。

Now the hard part.

现在才是难的部分。

I have spent the last week speaking to everyone involved to understand whether it really is possible to make this process more scalable.

过去一周,我一直在和所有参与者沟通,想弄清楚这个流程到底能不能更规模化。

We believe it is.

我们相信可以。

This will be the next chapter. It started with one dog. It will not end with one.

这将是下一章。它从一只狗开始,但不会止于一只。

I will have more to share soon.

很快会分享更多。

Best,

Best,

Paul

Paul

Everyone asks me how I did it. Here it is**

Part 1: Rosie's Story**

June 2023: About three years ago, I noticed something wrong with Rosie. She had swollen lumps on her head and leg, and it was noticeably bothering her. Over the course of the next 11 months I took her to a veterinarian three times. During each visit, the vet was dismissive and no cancer diagnosis was made.

May 2024: At this point, the swelling had become severe and started bleeding. I insisted that the vet address it. Rosie had surgery to remove the swollen masses and a biopsy was taken. This is when the cancer was finally diagnosed. Eleven months late.

The fatal prognosis left me with a choice: accept it, or throw everything I had at it. I used ChatGPT and devoured everything I could to understand cancer and what I could do about it. All the while continuing a full-time job: running an AI consulting business.

After the diagnosis and my early research, I discussed what to do with a new veterinarian. Rosie was initially put on:

  • Chemotherapy - very expensive.

  • Standard autologous immunotherapy - not effective.

July 2024: Desperate for better treatment options, I settled on a high-end veterinarian clinic. With great success, many large masses were removed by surgery. One large mass remained - it would have required amputation of the leg. I debated but decided against it.

The clinic was great but on-going treatment was unaffordable. On a friend’s recommendation, I arrived at Dr. Mina Ghaly, also a vet.

August 2024: Dr. Ghaly is one of the unsung heroes of this story. He was the only vet that was truly receptive to me - a "citizen scientist." This new vet was critical in facilitating much of what was to come. About this time my journey in understanding cancer drug development had just begun. I knew that AlphaFold had been touted for its ability to accelerate the discovery of targeted cancer therapies and I wanted to see if that was applicable to Rosie’s case. I queried ChatGPT deeper on this, and the first step it suggested was to get genomic sequencing of Rosie’s DNA and her cancer cells’ DNA.

September 2024–January 2025: With cancer continuing to spread unabated, a new therapeutic regimen was needed. ChatGPT o1 identified Professor Martin Smith at the University of New South Wales (UNSW) as the lead for genomic sequencing.

Using tissue that was collected in January, genomic sequencing employed here was not like a cheek swab with partial sequencing from 23andMe. This was a full and complete genome sequence and required specific preservation of the tissue and extracted DNA. I drove the tissue samples from the vet to the Garvan Institute myself. Pavel Bitter's team at the Garvan Institute played a critical role in extracting DNA for sequencing. The DNA was then couriered to UNSW's Ramaciotti Centre for Professor Martin Smith to do his sequencing work - one of the critical deep science steps that just a couple of decades ago would have cost over a billion dollars and is rapidly coming down in price, while getting much, much faster.

https://www.ccralliance.org/about

February–May 2025: With the raw DNA data in hand, data analysis began in earnest. Gemini, Grok, and ChatGPT were all used in arriving at a data transformation protocol. My team and I eventually found a mutation in the c-KIT gene, a known driver of mast cell cancer. AlphaFold 2 was used to model and understand Rosie’s mutated c-KIT protein - a step that would have required specialised experimental techniques like crystallography only 9 years ago.

June–July 2025: The goal was to use a ligand to switch off the c-KIT mutation and hence stop the unfettered cancer growth. With a prospective cancerous mutation identified, we now had two pathways to consider:

But first, what is a ligand ? → Any molecule that binds specifically to a larger "target" molecule (usually a protein) to serve a purpose

(A) Using genetic algorithms - a numerical optimisation technique - to discover a novel ligand. Pulling together more scripts and simulation engines, we developed a candidate that worked in simulation. It could have taken years to go from petri dishes, to mouse models and finally to dogs. After further consideration, the risks and approvals process for a novel ligand made this approach unworkable within Rosie's timeframe. But the ligand candidate still exists - and if the approvals landscape ever catches up, it may yet have its day.

(B) Docking a library of pre-existing 1M+ ligands to look for a match. After two weeks of running 1 million candidates - eureka - a match! It felt like we finally had something that could work, but then this pathway began to unravel as well. The match was for an existing patented compound. This meant that there were huge legal barriers to use or synthesise the compound.

I did however make contact with the patent holder and seek a compassionate use exemption outside their existing legal pathways. Understandably this was too high a risk for them to consider and they declined.

This was a major low point. We had come so far - sequencing the healthy and cancerous DNA, running state-of-the-art tooling to develop candidates for treatment, identifying known compounds. It really felt like we had exhausted the space and it just was not meant to be.

August 2025: After two weeks of prioritising quality time with Rosie, an idea came to me - “what if it was possible to create a vaccine myself?” I spent the night with ChatGPT debating possibilities. Eventually we arrived at what looked like the best bet: a peptide neoantigen vaccine.

The vaccine approach is a fundamental shift from ligand docking; rather than merely obstructing the proteins that fuel cancer growth, vaccines enable the immune system to re-identify and actively eliminate cancerous cells.

I emailed Professor Martin Smith at UNSW's Ramaciotti Institute and he referred me to Dr. Deborah Burnett. Dr. Burnett said that while she did not have experience in peptide neoantigen vaccines, she did have experience with mRNA vaccines. This is yet another example of the ideation bouncing between humans and chat bots that was critical to the process. Following this advice from Dr. Burnett, I reverted back to ChatGPT and got confirmation that the mRNA approach would be faster.

Two pipelines were initiated in parallel:

  • mRNA vaccine construct development

  • mRNA vaccine ethics approval

September–mid October 2025:

Vaccine development:

Around early September, a fast-growing tumour needed to be removed. This was an opportunity for RNA extraction and sequencing.

Here we go again: tissue on ice, Pavel Bitter's team at the Garvan Institute, RNA couriered to UNSW, sequencing by Professor Martin's team at UNSW's Ramaciotti Centre.

Returning to the data analysis, we narrowed the field to 7 epitopes highly prevalent in both the mRNA and DNA. This intersection was the “smoking gun.” Because mRNA expression reveals the cell’s actual protein production, these 7 targets represent the most viable candidates for triggering a robust immune response.

To give you a flavour of being in my shoes, try asking your favourite LLM chat bot to list 7 random epitopes. For illustration purposes only, here are 7 random epitopes I got from Gemini:

And, here is one vaccine construct that I got from Gemini by merely passing the epitopes listed above and asking it to create one. Note that the construct is not unique, and depends on what one is optimising for:

PADRE—GPGPG—WITQCFLPVFLAQP—GPGPG—GVGSPYVSRLLGICL—AAY—KVAELVHFL—AAY—FLWGPRALV—AAY—SLLMWITQC—AAY—KIFGSLAFL

Try creating your own vaccine construct using your preferred chat bot of choice !

For the Rosie-specific case, I utilised Gemini 2 Pro to architect the multi-epitope vaccine construct, incorporating optimised linkers and adjuvants. The resulting sequence was then subjected to a secondary heuristic refinement via Grok 3, ensuring structural stability and minimising junctional immunogenicity.

DISCLAIMER: The vaccine construct listed above is strictly for educational purposes and is not indicated to be used for the purposes of drug development or as part of any treatment protocols.

Ethics approval (September–mid October 2025):

Navigating the ethics approval process was a second full-time job, demanding 120 hours of paperwork alongside my actual career. To manage the load, I turned back to chat bots for a massive tactical shift. I used them to decode the subtle legalese and opaque regulatory language necessary to secure permission for the trial.

The University of New South Wales was able to develop the vaccine but did not have a process for a trial of this "n=1" kind. To create a new process would have taken until mid-2026. Rosie did not have time.

My efforts to this point had already been considered unusual. UNSW and some other local media published them in July 2025 (albeit without the global fanfare). However, some experts were watching. I had managed to get the attention of Dr. Mari Maeda of the Canine Cancer Alliance in the USA - arguably the world's foremost authority on canine cancer.

Dr. Maeda connected me with Professor Rachel Allavena at the University of Queensland. Professor Allavena had an existing compatible trial approval. On hearing the news over a Google meet, I acted nonchalantly - glad the trial could go ahead. My real reaction after the call, was fist pumping so hard Rosie's fear of thunder was almost provoked.

October–November 2025: With the trial paperwork completed, Professor Pall Thordarson and his team at UNSW could now commence manufacturing the vaccine. After 6 weeks of their expert work, the vaccine was ready.

December 2025: Go time. Rosie jumped into the car and we headed north. We took the 10-hour drive to Queensland to commence treatment. However, unbeknownst to me, the relevant campus was another four hours' drive out of Brisbane.

Finally at the University of Queensland’s School of Veterinary Science, we were ready to proceed:

  • A specifically designed mRNA vaccine - a precision-guided weapon to strike the cancer, developed with a pipeline designed by ChatGPT o1, implemented for candidate development by Gemini Pro 2, and with the final design validated by Grok 3 Thinking.

  • Supporting drugs to weaken the cancer's defences - without these, mRNA vaccines effectively just bounce off or are rendered useless before they can hit the cancer.

January 2026: Three weeks in, the cancerous areas swelled up - actually a good sign. Pseudoprogression. It means the T-cells are swarming.

Six weeks in, two cancerous areas were shrinking.

February 2026: The two areas, specifically around Rosie's legs, were returning to what appeared normal. Residual flat bumps from now presumably dead cancer cells remained, i.e., scar tissue.

Despite the tumors on Rosie’s legs receding in size, there was still a growing mass on Rosie's rear. This mass was surgically removed and sent again for genomic analysis.

March 2026: March 8th - the data from the non-responsive tumour arrived, analysis commenced.

March 10th - early signs suggested there were differences in the non-responsive cancer compared to the one the vaccine was designed for.

March 11th - the story broke in Australia.

March 12th - the story ignited X.

The last week has been a whirlwind. Three years ago I saw that Rosie needed help. I did everything I could. I was fortunate to have a background in machine learning and win the trust of world leading experts who saw something worth pursuing.

The pace at which these events transpired could not have been possible without AI chat bots.

Part 2: The AI Story

Let me address the debate about what AI actually did.

This was not an upload of DNA to ChatGPT with the prompt: "Please make a vaccine with no mistakes."

It took months. It required ChatGPT, Gemini, and Grok - each for different things at different stages.

The hardest work done by AI - the core science: turning raw genomic data into a vaccine prescription.

We started with ~300 gigabytes of raw sequencing data - whole genome sequencing of Rosie's tumour and a matched normal blood sample, plus later RNA sequencing of the tumour. The final output was roughly half a page: an mRNA vaccine construct encoding 7 neoantigen targets.

As a non-biologist, I relied on chat bots to help me design a bioinformatics pipeline. I also worked with chat bots extensively to implement it.

These are the specific tools for people wanting to understand the process. For most readers this list will probably raise more questions than answers. It took me months to wrap my head around them, and I had the benefit of working on this for over a year at that point. So without further ado, the critical components:

  • BWA-MEM for alignment

  • GATK Mutect2 (a Bayesian somatic model) for variant calling

  • Ensembl VEP for annotation

  • pVACseq with NetMHCpan-4.1 - a neural network that predicts whether a mutant peptide will bind to Rosie's specific immune molecules (DLA alleles)

What I have come to understand is that these are the same class of tools used in human precision oncology pipelines.

We then validated the DNA-predicted targets against RNA sequencing data to confirm the mutations were actually being expressed by the tumour. Only epitopes with confirmed RNA expression were retained. These epitopes became the vaccine construct that I sent to the lab for synthesis.

The implementation and use of these tools are probably the substance of graduate and postdoc activity in various institutes. I do not think everyone should have to know what I know to be able to use these tools. I think this was far more complex than it needed to be.

So what did the chat bots actually do?

They were indispensable - but not in the way people assume.

  • Planning & pipeline design: I used ChatGPT and Gemini to map out the entire bioinformatics workflow - what tools to use, in what order, what the inputs and outputs should be.

  • Troubleshooting: When tools failed (and they failed constantly - dependency conflicts, reference genome incompatibilities, annotation format mismatches), we used chat bots to debug. The dog genome is far less well-annotated than the human genome, and many tools assume human data. Every step had friction.

  • Candidate filtering & construct design: Grok helped filter our epitope candidates and later helped convert the final confirmed targets into the mRNA vaccine construct - the actual sequence with linkers, UTRs, and codon optimisation for canine cells.

  • Treatment protocol design: ChatGPT and Gemini helped design the multimodal protocol - working through drug interactions, timing, immunological synergies, and the phased rollout of distinct therapies. This involved weeks of iterative analysis across pharmacology, tumour immunology, and veterinary oncology.

  • Education: I am not a biologist. The chat bots taught me what cancer is at a molecular level, what neoantigens are, what MHC/DLA molecules do, what truncal vs branch mutations mean, what the tumour microenvironment is, and why any of this matters.

  • Ethics, compliance & coordination: The chat bots helped me write the ~100 pages of ethics approval documents, navigate the regulatory landscape across Australian states, and coordinate with multiple universities.

The vaccine was not given alone.

The chat bots also helped design a multimodal treatment protocol - not just the vaccine, but the entire immunological strategy around it:

  • A personalised mRNA neoantigen vaccine - encoding 7 targets designed to train Rosie's T-cells to recognise and kill her specific cancer cells

  • A tyrosine kinase inhibitor - targeting Rosie's c-KIT mutation, providing foundational anti-tumour pressure and modulating the tumour microenvironment

  • A PD-1 checkpoint inhibitor - removing the brakes from Rosie's T-cells, unleashing their full killing potential against the cancer

I have seen a lot of commentary online suggesting it was really just the PD-1 inhibitor doing the heavy lifting, or just the tyrosine kinase inhibitor. This misunderstands how cancer actually works. A tumour does not just sit there waiting to be killed - it actively builds a suppressive microenvironment around itself, corrupting nearby immune cells, growing its own blood supply, and hiding from the immune system.

If this were Star Trek, the cancer tumour microenvironment is the ship's shields. You can fire as many photon torpedoes - mRNA trained T cells - as you want. If the shields are up, nothing gets through.

No single therapy punches through cancer’s “shields” alone. The tyrosine kinase inhibitor and the PD-1 inhibitor take the shields down - but from different angles.

The TKI targets the tumour's supply infrastructure. Cancer needs blood vessels to feed itself and it actively grows new ones - a process called angiogenesis. The TKI blocks this, starving the tumour of nutrients and oxygen. It also directly inhibits the c-KIT mutation driving the cancer's growth signal. In Star Trek terms, it is disabling the enemy's engines and cutting power to life support.

The PD-1 inhibitor works on a different problem entirely. Cancer cells display a protein on their surface that sends a "stand down" signal to any mRNA trained T-cell that approaches - essentially telling the immune system's soldiers to holster their weapons. The PD-1 inhibitor blocks that signal, so the T-cells can no longer be fooled into backing off. If the TKI is taking down the shields from the outside, the PD-1 inhibitor is disabling them from within - shutting down the tumour's ability to cloak itself from the very cells sent to destroy it.

Firing these two together: the TKI & PD-1 - the shields come down and the mRNA trained T-cell photon torpedoes get through.

The sequencing and timing of these therapies mattered enormously - you can not give immunosuppressant treatments, TKI’s & PD-1’s alongside an immune-activating mRNA vaccine. ChatGPT and Gemini helped me work through the pharmacological interactions, tapering schedules, and phased rollout across weeks of back-and-forth.

What the chat bots did NOT do:

They did not collect samples. They did not isolate or sequence the DNA. They did not physically manufacture the vaccine. They did not administer it. Many brilliant scientists were required - including Professor Pall Thordarson at the UNSW mRNA Institute who manufactured the vaccine, Professor Rachel Allavena & Dr. José Granados at the University of Queensland who administered it, and Professor Martin Smith who provided expert guidance on the bioinformatics throughout.

In summary:

The chat bots empowered me as an individual to act with the power of a research institute - planning, education, troubleshooting, compliance, and yes, real scientific design work in converting genomic data to a vaccine prescription and designing the treatment protocol around it. But they worked alongside humans at every step. The combination is what made it possible.

https://www.abc.net.au/listen/programs/healthreport/dog-owner-ai-cancer-treatment/105462166

Part 3: What is next

Since Rosie's diagnosis, I have done everything I can to help her. But the reaction to this story - the outpouring of support, the thousands of messages from people with dogs in distress - has made something clear.

Rosie received a fully individualised, multimodal mRNA cancer protocol. One dog, one vaccine, designed from scratch. Three months in, she is showing strong signs of improvement.

That was the easy part.

What I keep coming back to is this: I do not know why I had to be this obsessed to get here. There are so many unnecessary barriers. So many techniques and tools that could be made far easier to access. The science exists. The AI exists. The gap is in making it reachable.

For years, I have discussed with friends what kind of AI company I should start. About 3 months ago, one of them said - "why are you even asking that question? Surely it is helping other people do what you did for Rosie." At the time, I was not convinced. I had done a lot, and it had given me more options to try, but there had been no breakthrough. Now, three months into treatment, Rosie is improving. And the response from the community has been overwhelming.

Now the hard part.

I have spent the last week speaking to everyone involved to understand whether it really is possible to make this process more scalable.

We believe it is.

This will be the next chapter. It started with one dog. It will not end with one.

I will have more to share soon.

Best,

Paul

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