我們的基因演化是為了抵禦古老的威脅，但在現代社會，其中一些變化可能對我們不利

 Recently The New York Times reported the following:

Where Do Autoimmune Diseases Come From? (2/2)

Our genes evolved to fight ancient threats, but in the modern world, some of those changes may be turning against us.

By David Quammen (David Quammen is a science journalist and author of 19 books. This piece is part of “Disease States,” his new series on evolution and disease.)

Published Oct. 20, 2026, Updated Oct. 22, 2026

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Today, according to the researchers, those same gene variants seem to be having an opposite effect. With infectious diseases better controlled and the prevalence of M.S. on the rise, “we again observe a striking correlation with changes in our environment, including lifestyle choices and improved hygiene, which no longer favours the previous genetic architecture,” they wrote. In other words, genes that once protected us may now put us at risk.

Another study from an international team of researchers looked at a more recent historical moment of abrupt demographic change: the Black Death. This 14th-century pandemic of plague (caused by the bacterium Yersinia pestis, which is carried by fleas, which are carried by rats) swept through Europe, the Middle East and northern Africa between 1346 and 1353, killing as much as 30 to 50 percent of the population in those areas.

The researchers scrutinized DNA sequences from the dead in England and Denmark, some buried just before the plague years, some during and some after. One of their sources was East Smithfield, a Black Death mass burial site just east of the Tower of London. There and elsewhere, the researchers found four immunity-related gene variants in the genomes of more people buried after the plague than before or during it, suggesting that those variants had conferred a survival advantage. After a dispute of their mathematical methods by another team, the researchers refocused their assertion on one variant. That variant, evidently adaptive against plague, is now a known risk factor for Crohn’s disease. So it seems that the Black Death, like the transition to pastoralism during the Bronze Age, may have been a selective event that increased the jeopardy of future generations to autoimmune diseases.

Although the Oxford team, in its study of M.S., called this situation a case of outdated “genetic architecture,” there’s another metaphor that makes the same point more vividly. Recall the adage about the failings of military leadership: that generals spend their peacetime preparing to fight the last war, rather than the next one. They cling to obsolete tactics and strategies and weaponry — things that worked well in the past — despite the march of time and the arrival of novelties. This is apparently what evolution has done with the gene variants that many of us carry today. Autoimmune diseases in the 21st century may represent the human immune system’s efforts to fight a war that was once cataclysmic and is now less so against ubiquitous and incurable infectious diseases.

For some people, the miseries of M.S. or lupus or other autoimmune maladies is a cruel misfortune. Others are luckier. For instance, me: I have only my psoriasis (inherited from my father, who inherited it from a lineage of Norwegian country people) as a reminder that my own immune system is ready and eager, too eager, to fight the last war — the war between a Bronze Age herdsman and a virus he picked up from one of his goats.

Translation

自體免疫疾病從何而來？ （2/2）

我們的基因演化是為了抵禦古老的威脅，但在現代社會，其中一些變化可能對我們不利

（繼續）

如今，研究人員表示，同樣的基因變異似乎產生了相反的影響。隨著傳染病得到更好的控制，多發性硬化症（MS）的盛行率不斷上升，他們寫道:「我們再次觀察到，這些疾病與環境變化之間存在顯著的相關性，包括生活方式的選擇和衛生條件的改善，而這些變化不再有利於先前的基因結構」。換句話說，曾經保護我們的基因現在可能使我們面臨風險。

另一項由國際研究團隊進行的研究則著重於近期歷史上人口急劇變化的時期：黑死病。 14世紀的鼠疫大流行（由鼠疫耶爾森菌引起，菌由跳蚤攜帶，跳蚤又被老鼠攜帶）在1346年至1353年間席捲歐洲、中東和北非，導致這些地區30%至50%的人口死亡。

研究人員仔細分析了英格蘭和丹麥死者的DNA序列，其中一些死者埋葬於鼠疫爆發前，一些埋葬於鼠疫期間，還有一些埋葬於鼠疫之後。他們的樣本來源之一是East Smithfield，這是位於倫敦塔東側的黑死病萬人坑。研究人員在那裡以及其他地方發現，在鼠疫之後埋葬的人的基因組中，有四種與免疫相關的基因變異，而鼠疫之前或期間埋葬的人的基因組中則沒有這種變異，這表明這些變異賦予了他們生存優勢。在另一研究團隊對他們的數學方法提出質疑後，研究人員將研究重點重新放在其中一種變異上。這種變異顯然具有抵抗鼠疫的適應性，如今已被證實是克隆氏症的已知風險因素之一。因此，黑死病似乎就像青銅時代向畜牧業的過渡一樣，可能是一種選擇性事件，增加了後代罹患自體免疫疾病的風險。

儘管牛津大學的研究團隊在對多發性硬化症 (MS)的研究中將這種情況稱為過時的“基因結構”，但還有另一個比喻能更生動地表達同樣的觀點。想想那句關於軍事領導失敗的諺語：將軍們在和平時期為最後一場戰爭做準備，而不是之後的戰爭。他們固守過時的戰術、戰略和武器 - 那些過去行之有效的方法 - 儘管時代在變遷，新事物層出不窮。這顯然就是進化對我們許多人今天攜帶的基因變異所做的。 21世紀的自體免疫疾病可能代表人類免疫系統試圖對抗一場曾經災難性的戰爭，一場曾經是災難性的戰爭，如今對抗的是無所不在且無法治癒的傳染病，這場戰爭的災難性後果已經減輕。

對某些人來說，多發性硬化症、紅斑性狼瘡或其他自體免疫疾病所帶來的痛苦是一種殘酷的不幸。有些人則幸運得多。例如我：我只有銀屑病（遺傳自我父親，而他又是從挪威鄉村家族遺傳的），它提醒自己的免疫系統隨時準備著，甚至過於渴望地去打那場戰爭- 一場青銅時代牧羊人與他從山羊身上感染的病毒之間的戰爭。

              So, evolution doesn’t have purposes, only results. Darwinian natural selection doesn’t shape creatures to be “better” or “higher” in some objective, transcendent sense — it shapes creatures to succeed in the here and now. And what works in one environment or period of time may prove harmful in another. More specifically, scientists have found evidence of natural selection for certain gene variants during the Bronze Age. Those same variants may increase the risk of autoimmune disease in people who carry them today. Apparently, the Black Death, like the transition to pastoralism during the Bronze Age, may have been a selective event that increased the chance for future generations to have autoimmune diseases.

Note:

1. MS is Multiple Sclerosis (多發性硬化症). It is used in the context of evolutionary medicine to describe a chronic autoimmune disease where the body's immune system mistakenly attacks the central nervous system. The attacks explain how gene variants that once protected ancient humans from infectious diseases have now become risk factors for developing Multiple Sclerosis due to modern hygiene and lifestyle changes.

癌症疫苗是美國國立衛生研究院的下一個「重大押注」（2/2）

Cancer Vaccines Are the N.I.H.’s Next ‘Big Bet’ (2/2)

New details have emerged about an initiative that starts in December to fast-track the vaccines, similar to the successful push for the Covid-19 vaccine.

The NYT - By Gina Kolata

Oct. 9, 2026

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Though the public-private partnership will draw inspiration and lessons from the global development of the Covid-19 vaccine, the timeline for the cancer vaccines will be nowhere near as fast. Phase 1 of the initiative, which will consist of small studies, is expected to take about three years and lead to “go-to information on different technical approaches to vaccines,” Dr. Letai said.

Larger trials in Phase 2 are expected to take at least four years, involve a national network of clinical trial sites and lead to definitive results. The ultimate goal, Dr. Adam said, is that “in seven to 10 years, anyone who walks into a doctor’s office can get a vaccine.”

That is still faster than would be expected without the initiative where it can take eight to 15 years to get F.D.A. approval, Dr. Adam said. And work would have been fragmented and uncoordinated.

It was small, fragmented studies with promising results that inspired the initiative.

They included, for example, one involving patients with kidney cancer that was led by Dr. Catherine J. Wu of the Dana-Farber Cancer Institute and her colleagues. The researchers took tumor cells from patients with advanced kidney cancer at the time of their initial surgery. Then, for each patient, they created a vaccine designed to attack the tumor’s unique mutations.

It is impossible to know if the patients were entirely cured in such a small study, but all nine were cancer-free after 40 months. Ordinarily, 30 to 50 percent would have relapsed within two years.

Dr. Wu and her colleagues are now developing vaccines for patients with glioblastoma, as well as for those with ovarian cancer.

Another encouraging early study focused on pancreatic cancer. Even with the best treatments, close to 90 percent of patients die within five years, said Dr. Vinod Balachandran of Memorial Sloan Kettering Cancer Center.

His group conceived the idea for a small study in 2017 and began it in 2019. When a patient had surgery to remove their pancreatic cancer, the investigators collected tumor tissue and shipped it to Genentech and BioNTech, a company that later produced Covid vaccines. The companies pinpointed the mutations unique to a patient’s cancer and then made a customized vaccine.

The investigators treated 16 patients and followed them for up to six years. Seven out of eight who responded to the vaccine are still alive, compared with just two out of the eight who did not respond.

That initial study, though — promising as it was — was not definitive.

“We cannot prove that vaccines are making patients live longer,” Dr. Balachandran said. His group and its industry partners began a much bigger study in 2023, enrolling 260 patients.

Based on what he has seen so far, Dr. Balachandran is hopeful about the future of vaccine therapy. With pancreatic cancer, he took on a cancer thought to be impervious to immune system attacks: “If we crack the toughest nut,” he said, “we can crack the rest.”

Translation

癌症疫苗是美國國立衛生研究院的下一個「重大押注」（2/2）

一項旨在加速癌症疫苗研發的計劃將於12月啟動，其模式與成功推動新冠疫苗研發的模式類似。該計劃的最新細節已經浮現

（繼續）

儘管這項公私合作計劃將從全球新冠疫苗的研發中汲取靈感和經驗，但癌症疫苗的研發速度遠不及新冠疫苗。Letai 博士表示該計劃的第一階段將包括一些小型研究，預計耗時約三年，並導致「成為關於不同疫苗技術方法的參考資訊」。

第二階段的大規模試驗預計至少需要四年時間，將涉及一個覆蓋全國的臨床試驗中心網絡，並最終得出確切結果。Adam 博士表示，最終目標是「在七到十年內，任何走進診所的人都能接種疫苗」。

Adam 博士說，即便如此，速度仍然比在沒有這項計劃下預期的要快得多，因為如果沒有這項計劃，獲得 FDA 批准可能需要8到15年。而且，如果沒有這項計劃，工作將會非常分散且缺乏協調。

正是那些取得令人鼓舞的小型、分散的研究成果促成了這項計劃的誕生。

例如，其中一項研究涉及腎癌患者，由 Dana-Farber 癌症研究所的 Catherine J. Wu 博士及其同事領導。研究人員在患者首次手術時從晚期腎癌患者身上提取了腫瘤細胞。然後，他們為每位患者開發了一種疫苗，旨在攻擊腫瘤特有的突變。

在這樣一項小型研究中，我們無法確定患者是否完全治愈，但所有九名患者在40個月後均未出現癌症復發。通常情況下，30%到50%的患者會在兩年內復發。

Wu博士及其同事目前正在研發針對膠質母細胞瘤和卵巢癌患者的疫苗。

另一項令人鼓舞的早期研究聚焦於胰臟癌。Memorial Sloan Kettering 癌症中心的 Vinod Balachandran 博士表示，即使接受最好的治療，近90%的患者也會在五年內死亡。

他的團隊在2017年構思了一項小型研究，並於2019年啟動。當患者接受胰臟癌切除手術時，研究人員會收集腫瘤組織並將其送到 Genentech 和 BioNTech， 即那家後來研發出新冠疫苗的公司。這兩家公司會確定患者癌症特有的突變，然後研發度身定做的疫苗。

研究人員對16名患者進行了治療，並對他們進行了長達六年的追蹤。 8名對疫苗有反應的患者中，7名仍存活；而8名沒有反應的患者中，只有2名仍存活。

然而，這項初步研究 - 儘管前景可觀 - 卻並非是最終定論。

Balachandran 博士說: 「我們無法證實疫苗是能真的延長患者的壽命」。他的團隊及其產業夥伴於2023年啟動了一項規模更大的研究，招募了260名患者。

根據目前所見，Balachandran 博士對疫苗療法的未來充滿希望。他曾攻克胰腺癌，這種癌症一度被認為能抵禦免疫系統攻擊的癌症 - 他說:“如果我們能攻克最難攻克的難題”，“我們就能攻克其他難題。”

              So, a new type of cancer treatment by using vaccines is so promising that it demands a national effort to expedite researches that will involve many medical institutes in the US to work together to develop and test the new vaccines. The ultimate goal is that in seven to 10 years, anyone who walks into a doctor’s office can get a vaccine. Apparently, this is good news for everyone.

Note:

1.Genentech and BioNTech are two separate, independent companies. Although they have partnered on major medical research projects, they have completely distinct corporate identities, history, and parent structures. The two companies are frequently mentioned together because they entered into a high-profile, multi-million-dollar strategic collaboration to co-develop individualized mRNA-based cancer immunotherapies. (Google)

人工智能聰明了，但人類智能蠢了

Recently Jacky FUNG 馮智政 in his Patron published the following:

Education｜人工智能聰明了，但人類智能蠢了

By Jacky FUNG 馮智政

Jacky FUNG 馮智政 Patron (https://www.patreon.com/jackyfungcc/posts/education-ren-170778249)

Mon, Sep 28 at 3:40 p.m.

國際學生能力評估PISA 2025 創新低，科技融入學習做錯嗎？

人工智能在今年上海國際數學奧林匹克考得滿分。同一時間，經合組織公布 #PISA2025：經合組織國家十五歲學生的閱讀、數學、科學平均分，三科同創有紀錄以來最低¹。閱讀十年跌了28分，按經合組織「約20分等於一年學習進度」換算，等於少讀了一年半書。三科都達不到基本水平的學生，由三年前每六個一個，升至每五個一個¹。

01/

跌在哪裡，比跌了多少更値得留意。讀得快、答得錯的「急讀」學生，七年間接近倍增至9%；超過三分一學生查證過資料來源，最後仍然選擇相信直覺¹。這不是學少了，而是讀書的方式變了，補習加操解決不了。

❚ ❚ 問題在AI出現前已經開始

02/

第一個原因是屏幕本身。多項整合研究發現，紙本閱讀的理解程度一直勝過屏幕，而且2000年後進行的研究差距更大，數碼原住民一樣輸；更麻煩的是，在屏幕上閱讀的人，還會以為自己明白了²。

這並非新發現。經合組織早在2015年已經警告，在學校電腦上花大錢的國家，成績沒有改善³。十年後，瑞典掉頭買回印刷書⁴。

屏幕之外，專注力亦同時被拆走。資訊學教授Gloria Mark追蹤上班族近二十年，人在屏幕前停留而不轉走的時間，由2004年的兩分半鐘縮至47秒⁵。讀懂一篇教材，需要的專注以小時計。

❚ ❚ 用AI做功課的真正代價

03/

經濟學者Strömberg、Lei與Wu追蹤兩萬六千多名中國中學生，發現用AI做功課後，功課分數升了18%，半年內月考卻跌了20%⁶。

受創最深的，竟是成績最好的三分一，跌幅達24%。

但損失並非人人有份，而是集中在約八成「外判功課」的學生身上：做得特別快、分數特別高的那一批⁶。PISA看到同一件事：用AI代勞的學生成績偏低；每週用一兩次輔助學習的，與不用者相若；經常使用而又學過分辨AI真偽的，才稍勝一籌¹。AI不是捷徑，最好的情況，只是沒有蝕，再加一點。

分野不在用不用AI，而在省下的時間去了哪裡。本來要90分鐘的功課，40分鐘做完，多出來的那一截，是誰替你想的？

省下的時間，就是被外判的思考。

❚ ❚ 揀學校，應該問甚麼

04/

經合組織教育總監Andreas Schleicher點名南韓，形容其科技運用更深思熟慮、更有意圖，用法由教師設計⁷。這份克制由來已久：2015年，南韓學生每日在校用電腦只有9分鐘，不到澳洲的六分之一³。

以後揀學校，就不要只問有多少部機械人、多少部3D打印機，要問兩件事：功課的設計，有沒有令學生非花時間不可；AI的用法，由老師設計，還是由學生自決。

PS：人工智能愈來愈聰明，學生的智能愈來愈薄弱，到時誰是贏家，誰是輸家？

¹ OECD, PISA 2025 Results (Volume I), 2026；Country Note: Hong Kong (China) ² Delgado et al., Educational Research Review, 2018；Clinton, Journal of Research in Reading, 2019 ³ OECD, Students, Computers and Learning: Making the Connection, 2015 ⁴ 美聯社，2023年9月 ⁵ Gloria Mark, Attention Span, 2023 ⁶ Strömberg, Lei & Wu, The Generative AI Learning Penalty, CEPR Discussion Paper No. 21577, 2026（未經同行評審） ⁷ Financial Times，2026年9月8日 ⁸ Smartphone Free Childhood, Parent Pact, 2024（簽署數字為機構自報）

(Source: https://www.patreon.com/jackyfungcc/posts/education-ren-170778249)

Comment:

So, it is noted that PISA 2025 scores hit a new low; did we make a mistake in integrating technology into learning? The article suggested that the problem started before the advent of AI. The first reason is the screen itself. Analyses have found that reading comprehension on paper has consistently outperformed screens. It is also shocking to note that this is not a new discovery. As early as in 2015, the OECD warned that countries spending large amounts of money on school computers saw no improvement in academic performance. A decade later, Sweden reversed course and brought back printed books. Apparent, printed media still has it value.

Note:

1. Jacky Fung Chi Ching (馮智政) is a prominent Hong Kong think-tank researcher, political commentator, and media host. He holds a master's degree in International Relations from HKU and pursued a doctorate in Education at CUHK. Fung has worked extensively with institutions like the Hong Kong Policy Research Institute and the Roundtable think tank. Widely recognized for his sharp socio-political analysis, he has hosted popular radio and television programs, including Commercial Radio Hong Kong's Guan Ming Ding. Currently based in the UK, Fung continues to engage audiences globally through his analytical YouTube platform, the Sinic Political and Economic Channel. (Google)

這種罕見基因會顯著增加從未吸煙者罹患肺癌的風險（1/2）

Recently The New York Times reported the following:

This Rare Gene Drastically Raises Lung Cancer Risk in People Who Never Smoked (1/2)

The gene is found predominantly in Southern Appalachia and may be one of the most powerful cancer-risk mutations ever found.

The NYT - By Gina Kolata (Gina Kolata reports on diseases and treatments, how treatments are discovered and tested, and how they affect people.)

Sept. 17, 2026

Between 200 and 225 years ago, someone or several someones from the British Isles had a gene mutation that caused lung cancer. They traveled to America, settled in Southern Appalachia and transmitted the cancer gene to their descendants and their descendants’ descendants.

Today that lung cancer gene, known as EGFR T790M, is found largely in residents of the United States and mostly in Southern Appalachia, especially Tennessee and Alabama. It makes lung cancer 62 times as likely in those who have never smoked and 10 times as likely in smokers.

Those are among the stunning findings of a new report, published on Thursday in Science by researchers at the Dana-Farber Cancer Institute and 23andMe Research Institute.

The gene is one of the most powerful, if not the most powerful, cancer-risk mutations ever found, said Alexander Gusev, a geneticist at Dana-Farber and an author of the paper.

Unlike other cancer genes that can cause cancer in a variety of organs, this gene is associated only with lung cancer. Researchers expect their discovery can help unlock secrets about the development of the disease.

For those with the gene, the hope is for early detection and treatment or even cancer prevention, said Dr. Raymond DuBois, the director of the Medical University of South Carolina’s Hollings Cancer Center, who was not associated with the work.

“This is a great story,” Dr. DuBois said, adding that he “read the paper like a novel.”

The variant was discovered in 2005, but because it is so rare, researchers were limited to studying families in which several members had the gene and got lung cancer. Studies like that could not reveal how much the gene increased risk.

Investigators did learn, though, that the variant was unusual. Lung cancer patients often have mutations in the EGFR gene, but those mutations arose by random bad luck later in life. If those mutations arise in embryos, they kill the embryos. But not the EGFR T790M mutation. People are born with it, and it is not lethal. It causes only lung cancer, but decades later.

Dr. Jaclyn LoPiccolo and Dr. Pasi A. Jänne, lung cancer experts at Dana-Farber, realized that 23andMe’s data might hold the key to figuring out how dangerous EGFR T790M is. Other databases had too few people — less than a million participants, only a handful of whom had the mutation. But 23andMe, a direct-to-consumer recreational databank that many use to find ancestors, was huge.

The database had more than 10 million people who had consented to participate in research, including the 3.37 million who had provided both genetic data and information on whether they had lung cancer. There were 641 who had the mutation.

(to be continued)

Translation

這種罕見基因會顯著增加從未吸煙者罹患肺癌的風險（1/2）

該基因主要發現於美國 Appalachia 南部地區，可能是迄今為止的最強致癌基因突變之一

大約在 200 到 225 年前，來自不列顛群島的人一個或幾個的人是帶有一種導致肺癌的基因突變。他們遷移到美國，定居在 Appalachia 南部地區，並將這種致癌基因遺傳給了他們的後代以及其後代的後代。

如今，這種被稱為 EGFR T790M 的肺癌基因很大程度上存在於美國居民中，主要是在Appalachia 南部地區，尤其是田納西州和阿拉巴馬州。這種基因使從未吸煙者罹患肺癌的風險增加62倍，吸煙者罹患肺癌的風險增加10倍。

這些令人震驚的發現來自 Dana-Farber 癌症研究所和 23andMe 研究機構的研究人員於週四在《科學》雜誌上發表的一份新報告。

Dana-Farber 癌症研究所的遺傳學家、論文的作者之一 Alexander Gusev 表示，這種基因是迄今為止發現的最強大的癌症風險突變之一，甚至可能就是最強大的。

與其他可導致多種器官癌症的基因不同，這種基因僅與肺癌有關。研究人員希望他們的發現能幫助揭開肺癌發展的奧秘。

並未參與這項研究的南卡羅來納醫科大學 Hollings 癌症中心主任 Raymond DuBois 博士表示，對於攜帶這種基因的人來說，希望在於能夠早期發現並治療，甚至預防癌症。

DuBois 博士說：「這是一個很棒的故事」。他還補充說，他「像看小說一樣讀完了這篇報告」。

這種變異於2005年被發現，但由於其極為罕見，研究人員只能研究那些有多位成員帶有該基因並患有肺癌的家族。此類研究無法揭示該基因究竟增加了多少患病風險。

不過，研究人員確實發現這種變異很特殊。肺癌患者的 EGFR 基因通常有突變，但這些突變往往是晚年因隨機的厄運而偶然發生的。如果這些突變發生在胚胎時期，則會導致胚胎死亡。但EGFR T790M 突變並非如此。人們出生時就帶有這種突變，而且它並非致命。它只會導致肺癌，但通常是在數十年後。

Dana-Farber 癌症研究所的肺癌專家 Jaclyn LoPiccolo 博士和 Pasi A. Jänne 博士意識到，23andMe的數據或許能揭示 EGFR T790M 的危險程度。其他資料庫的人數太少 - 參與者不到百萬，其中只有極少數人帶有這種突變。但  23andMe 是一家面向消費者的休閒基因資料庫，許多人利用它來尋找祖先，規模非常龐大。

該資料庫擁有超過 1,000 萬名同意參與研究的人，其中包括 337 萬名同時提供了基因數據和是否患肺癌病的資訊。其中有 641 人帶有該突變。

（待續）

早期數據顯示人工智能產生的藥物或可延緩衰老

Recently The New York Times reported the following:

Early Data Indicates an A.I.-Generated Drug Could Slow Aging

Artificial intelligence was used to help develop a drug candidate, rentosertib, for a rare lung condition. Its maker says the drug also seems to reduce the biological hallmarks of age.

The NYT - By Cade Metz - Reporting from San Francisco (Cade Metz is a Times reporter who writes about artificial intelligence, driverless cars, robotics, virtual reality and other emerging areas of technology.)

Sept. 7, 2026

Last year, a clinical trial conducted by Insilico Medicine, a company that aims to accelerate drug discovery using artificial intelligence, indicated that one of its drug candidates could help treat patients suffering from a chronic lung disease.

Now, the company says that data from the same clinical trial shows a more intriguing possibility: that the drug could also slow the aging process.

The molecular structure of the drug, called rentosertib, was generated with the assistance of A.I. Results of the new study, published Monday in the journal Nature Biotechnology, show that the drug reduced the biological markers of age as measured by six “aging clocks,” a different kind of A.I. technology designed to predict a person’s morbidity and mortality.

This elaborate clinical trial is a milestone in the widespread effort to improve health care using the same A.I. techniques that underpin popular chatbots like ChatGPT and image generators like Midjourney. Insilico is just one of many start-ups, tech giants and academic labs working to accelerate drug discovery and hone other medical tasks with help from these methods.

The recent rise of aging clocks is helping to push these efforts beyond short-term treatments and into the realm of longevity research. These systems estimate how quickly a person’s body is aging — or even how quickly individual organs are aging relative to the rest of the body. But scientists continue to debate how much useful information these so-called clocks are able to provide.

While Insilico’s clinical trial shows the promise of several A.I. techniques, its drug candidate could still be years away from regulatory approval, even for use in sick patients. And the company has not yet tested its anti-aging effects in healthy patients.

“This drug looks encouraging,” said Eric Topol, a cardiologist and the author of the book “Super Agers.” “But we do not yet have a definitive trial to make the final judgment.”

Insilico began exploring the new wave of A.I. technologies more than a decade ago. Founded in 2014 by Alex Zhavoronkov, a Latvian-Canadian mathematician, physicist and biotechnologist, the company was among the earlier efforts to streamline drug discovery using what are called neural networks.

Using techniques similar to those that train A.I. systems like ChatGPT, Insilico first built a model to analyze a giant pool of data spanning health records for thousands of medical patients; blood tests describing the microscopic proteins created inside their bodies; and myriad academic papers detailing the effects of these proteins. With this system, the company is trying to identify particular proteins that lead to illness and disease.

Insilico then built a second system that analyzes troves of data describing the physical shape of proteins and the way these tiny biological mechanisms bind to other molecules. This system is designed to generate entirely new molecules that could bind to a particular drug target and neutralize its effects.

“It is like scanning a lock and generating a key that fits the lock,” Dr. Zhavoronkov said in an interview.

This is how he and his company developed rentosertib, which is meant to treat a disease called idiopathic pulmonary fibrosis, or I.P.F. Sometimes called “the Alzheimer’s of the lungs,” I.P.F. is a chronic disease that thickens and scars pulmonary tissue, reducing its ability to move oxygen into the bloodstream. The condition can lead to death, even within a few years.

Last year, with its clinical trial, Insilico showed that its drug candidate could significantly expand air capacity inside the lungs of patients who had I.P.F. But that was only part of the trial. Dr. Zhavoronkov said his company also designed the drug in an effort to generally extend a patient’s life span.

Separate from the tests involving I.P.F., the trial used six aging clocks to measure the markers of age in patients both before and after treatment with the drug. Across the 43 patients who participated in the trial, the clocks — which essentially try to predict a person’s age based on measurements of how well their cell, tissues and organs are functioning — showed significant reductions in the predicted age.

Each clock relies on a different analysis of those markers that yields a different prediction. During the trial, all six clocks showed a reduction in predicted age after patients took the drug for 12 weeks.

“This is the first study that shows, very clearly, that predicted biological age can be reduced,” said Vadim Gladyshev, a Harvard Medical School professor who helped build one of these aging clocks.

He acknowledged, however, that the study was far from conclusive, pointing out that the sample size was small and that aging clocks are not always reliable. Most notably, Insilico’s drug has not yet been tested in healthy patients: Because the company conducted its clinical trial solely with I.P.F. patients, the results could be unique to those with this particular condition.

But some experts believe that Insilico’s elaborate study could serve as a blueprint for future longevity research.

“These are methods we will use in future trials,” said Evelyne Bischof, a professor of medicine at Tel Aviv University who specializes in longevity.

Translation

早期數據顯示人工智能產生的藥物或可延緩衰老

人工智能被用於輔助開發一種名為 rentosertib 的候選藥物，用於治療一種罕見的肺部疾病。其研發者表示，該藥物似乎還能減少老化的生物學特徵。

去年，一家名為 Insilico Medicine 的公司進行的臨床試驗表明，該公司的一種候選藥物可能有助於治療慢性肺部疾病患者。 Insilico Medicine 致力於利用人工智能加速藥物研發。

如今，該公司表示，來自同一臨床試驗的數據顯示出更令人感興趣的可能性：該藥物或許還能延緩老化過程。

這種名為 rentosertib 的藥物的分子結構是在人工智能的輔助下產生的。這項週一發表在《自然·生物技術》雜誌上的新研究結果顯示，該藥物降低了六種「老化時鐘」所測量的生物年齡標記。 「老化時鐘」是一種人工智能技術，旨在預測人們的發病率和死亡率。

這項精心設計的臨床試驗是利用人工智能技術改善醫療保健這項廣泛努力的一個里程碑。這些人工智能技術也應用於 ChatGPT 等熱門聊天機器人和 Midjourney 等影像產生器。 Insilico 只是眾多致力於利用這些方法加速藥物研發，並改善其他醫療任務的新創公司、科技巨頭和學術實驗室之一。

老化時鐘的興起正推動這些研究超越短期治療，邁向長壽研究領域。這些系統可以估算人體老化的速度，甚至可以估算單一器官相對於身體其他部位的老化速度。但科學家仍在爭論這些所謂的「時鐘」究竟能提供多少有用的信息。

儘管 Insilico 的臨床試驗展現了多項人工智能技術的潛力，但其候選藥物距離獲得監管部門批准可能仍需數年時間，即使是用于重病患者。而且，該公司尚未在健康的受試者身上測試其抗衰老效果。

心臟病專家、《超級老齡者》(Super Agers)  一書的作者 Eric Topol 說: “這種藥物看起來很有希望”，“但我們還沒有進行最終的臨床試驗來做出最終判斷。”

Insilico 公司在十多年前就開始探索新一代人工智能技術。該公司由拉脫維亞裔加拿大籍數學家、物理學家和生物技術專家 Alex Zhavoronkov 於 2014 年創立，是早期利用神經網絡去使藥物研發流程達到更有效率的公司之一。

Insilico 公司採用類似於訓練 ChatGPT 等人工智能系統的技術，首先建立了一個模型來分析龐大的資料池，這些資料包括數千名患者的健康記錄、描述其體內產生的微小蛋白質的血液檢測結果，以及大量詳細闡述這些蛋白質作用的學術論文。利用這套系統，該公司正試圖辨識導致疾病的特定蛋白質。

隨後，Insilico 構建了第二個系統，用於分析海量數據，這些數據描述了蛋白質的物理結構以及這些微小的生物機制與其他分子的結合方式。這個系統是用來生成全新的分子，這些分子可以結合特定藥物的目標對像並消滅它。

Zhavoronkov 博士在一次採訪中說道: 「這就像先掃描一把鎖，然後造出一支可開啓它的鑰匙」。

他和他的公司正是利用這種方法開發了 rentosertib，一種用於治療特發性肺纖維化（IPF）的藥物。 IPF 有時被稱為 “肺部阿茲海默症” ，是一種慢性疾病，會導致肺組織增厚和形成疤痕，從而降低肺部將氧氣輸送到血液的能力。這種疾病甚至可能在幾年內導致死亡。

去年，Insilico公司透過臨床試驗表明，其候選藥物能夠顯著擴大特發性肺纖維化（IPF）患者的肺部容量。但這只是試驗的一部分。 Zhavoronkov 博士表示，該公司研發該藥物的另一個目的是延長患者的壽命。

除了針對IPF的試驗外，該試驗還使用了六種老化時鐘來測量患者在用藥前後各項年齡指標的變化。在參與試驗的43名患者中，這些時鐘 - 它們本質上是根據測量一個人的細胞、組織和器官運作情況來預測其屬於的年紀- 顯示預測的年齡有顯著降低。

每種老化時鐘都基於不同的指標分析方法，因此預測結果也不同。試驗期間，所有六種老化時鐘均顯示，患者服用藥物12週後，預測年齡有所降低。

曾參與建造了其中一個衰老時鐘的哈佛醫學院教授 Vadim Gladyshev 說道:「這是第一個研究非常清楚地表明預測的生物年齡是可以下降的」。

然而，他也承認這項研究遠未得出結論，指出樣本量較小，而且老化時鐘並非總是可靠的。尤其值得注意的是，Insilico公司的藥物尚未在健康的受試者中進行測試：由於該公司僅針對特發性肺纖維化（IPF）患者開展了臨床試驗，因此研究結果可能僅適用於患有這種特定疾病的患者。

但一些專家認為，Insilico 公司這項精心設計的研究可以為未來的長壽研究提供藍圖。

特拉維夫大學的專門研究長壽的醫學教授 Evelyne Bischof 說:「這些是我們在未來試驗將會採用的方法」。

So, a clinical trial conducted by Insilico Medicine has indicated that one of its drug candidates could help treat patients suffering from a chronic lung disease. Now, the company says that data from the same clinical trial shows a more intriguing possibility: that the drug could also slow the aging process. However, it is also acknowledged that the study is far from conclusive as the sample size is small and that aging clocks are not always reliable. Yet, Insilico’s study could probably serve as a blueprint for future longevity research.

Note:

1. The core idea of the book entitled Super Agers: An Evidence-Based Approach to Longevity written by Dr. Eric Topol is that science and technology have converged to create a breakthrough moment where we can significantly extend human "healthspan"—the number of years lived free from debilitating chronic disease—rather than just extending lifespan.  (Google)

90歲的「DNA之父」，為甚麼被科學界割席？

 Recently Simon Shen (沈旭暉) posted the following article on Patreon:

【國際關係日評】 90歲的「DNA之父」，為甚麼被科學界割席？

沈旭暉 Simon Shen (simonshen@creator.patreon.com)

 Sun, Sep 6 at 4:04 p.m.

6 Sept 2026

 James Watson 是20世紀最重要的科學家之一。1953年，他與 Francis Crick 提出 DNA 雙螺旋結構，後來與 Maurice Wilkins 共同獲得諾貝爾獎。今天我們談基因工程、DNA鑑證，都離不開這場科學革命。想不到到了晚年，Watson 卻因為另一套關於基因的理論 / 想法，被自己曾經領導的科學界集體割席。

2007年，Watson 公開表示黑人與白人在智力測試上的平均差異可能與遺傳有關，引起巨大爭議，最終離開領導多年的 Cold Spring Harbor Laboratory。2019年，已經90歲的 Watson 在 PBS 紀錄片再次被問到這個問題，仍然表示自己的看法沒有改變。Cold Spring Harbor 隨即褫奪他所有榮譽職銜，直指他的說法「沒有科學根據」。

Watson 是不是納粹或者今天所說的 far right？都不是。但他的思想確實具有明顯優生學色彩：他相信人類很多重要特徵受到遺傳影響，也不抗拒利用遺傳科技選擇某些特徵、避免另一些特徵。

一個破解 DNA 結構的諾獎得主這樣說，是否特別可信？起碼主流科學界認為「不是」。Watson獲得諾貝爾獎的研究，是 DNA 的分子結構和遺傳資訊如何傳遞，幫助我們了解基因如何運作，卻沒有證明「黑人與白人的平均智力差異由基因造成」。後者是另一個完全不同、而且複雜得多的命題。

換句話說，今天科學界並不否認智力受到遺傳因素影響，但一項特徵具有遺傳性，不代表不同群體之間的平均差異就是遺傳造成。最簡單的例子是南北韓：兩邊人口遺傳背景非常接近，但今天南韓年輕人的平均身高明顯高於北韓人。不是南韓人在兩三代之間突然進化出「高佬基因」，而是營養、醫療和成長環境不同所致。

智力比身高更複雜。教育、營養、家庭環境、收入、文化、甚至測量方法，都可能影響結果。因此由「智力具有遺傳性」，跳到「兩個族群的平均 IQ 差異是基因造成」，中間就缺少了最重要的一步，也就是缺乏 correlation。因此，Watson 晚年的爭議很諷刺：他最偉大的發現告訴我們基因非常重要，但他後來希望論證「群體差異可以由基因解釋」，卻處處碰壁，乃至接近身敗名裂。

(待續)

（第二部份繼續於）https://www.patreon.com/c/simonshen/posts?filters%5Btag%5D=%E5%9C%8B%E9%9A%9B%E9%97%9C%E4%BF%82%E6%97%A5%E8%A9%95)

I agree with the viewpoint that intelligence is more complex than height. Education, nutrition, family environment, income, culture, and even measurement methods can all influence the development of intelligence. Therefore, jumping from "intelligence is heritable" to "the difference in average IQ between two ethnic groups is caused by genes" misses an important link: to prove the correlation.

Note:

1. Simon Shen (沈旭暉) is a Hong Kong born international relations scholar, political commentator, and public intellectual. He is particularly known for his work and commentary on China's foreign policy, U.S.–China relations, nationalism, Hong Kong, Taiwan, and international politics. He studied at Yale University and subsequently obtained a doctorate in politics/international relations from the University of Oxford. He has held academic and research positions at universities and institutions in Hong Kong and overseas. (ChatGPT)

2. James Watson (1928–2025) was an influential American molecular biologist and geneticist. In 1953, he co-discovered the double-helix structure of DNA alongside Francis Crick, drawing on pivotal X-ray crystallography data. This landmark breakthrough revolutionized modern biology by demonstrating how genetic information is stored and replicated. For this achievement, Watson shared the 1962 Nobel Prize in Physiology or Medicine. Later in his career, he led Cold Spring Harbor Laboratory and directed the Human Genome Project. (Google)

科學家發現1,000多個與人格相關的基因變異（2/2）

Recently The New York Times reported the following:

Scientists Find More Than 1,000 Genetic Variants Linked to Personality (2/2)

More than one million genomes helped identify DNA variants linked to extroversion, agreeableness, neuroticism and more. Researchers measured how those traits influenced how people lived.

The NYT - By Emily Baumgaertner Nunn (Emily Baumgaertner Nunn is a national health reporter for The Times, focusing on public health issues that primarily affect vulnerable communities.)

Sept. 3, 2026

(continue)

“It was kind of a conspicuous absence,” said Dr. Tucker-Drob, whose academic work focuses on “individual differences,” a realm of psychology that examines the ways people diverge in their thoughts, feelings and behaviors. To him, personality is not just an abstract concept: The way people engage with themselves and the world can help determine how much money they make, the types of medical care they seek, and how strong their friendships are.

Personality is “meaningfully related to all sorts of outcomes that I think everyone in society values,” he said.

The research team scanned roughly 10 million genetic variants across the genome in order to map the “Big Five.” By aggregating disparate studies on various traits, researchers were able to uncover the ways personality predispositions rippled out into health, habits and lifestyle choices.

Researchers found 258 different genetic variants linked to extroversion, for example, a 15-fold increase in the number of variants previously known. A genetic profile with high extroversion seemed to reduce a person’s risk of anxiety, depression and post-traumatic stress disorder, all of which involve internalizing distress. But the trait was also linked to neurodevelopmental conditions such as A.D.H.D.

People who were predisposed to conscientiousness — or a capacity for productivity and organization — appeared more likely to exercise, choose low-calorie foods and sleep well. Genetic scores for conscientiousness helped predict who would move out of urban centers and into affluent suburbs by age 50.

Neuroticism, which is defined as a tendency toward emotional instability, was predictably correlated with 10 different psychiatric disorders, plus a higher body mass index and increased rates of smoking. Study participants with genetic profiles high in neuroticism seemed to second-guess themselves in real time, frequently selecting options such as “I don’t know” on research survey questions.

Since neuroticism can be a strong predictor of mental illness, some researchers are particularly interested in how the new findings illuminate possible triggers and avenues of disease. Dalton Conley, a sociologist at Princeton University who was not involved in the research, was particularly intrigued by the way the consortium’s results challenged a long-held theory among psychologists that neuroticism is primarily driven by differences in serotonin levels. Depression and anxiety are often successfully treated with medications that boost the chemical.

The new analysis showed that neuroticism variants were indeed especially active in brain cells — but revealed nothing pronounced about the serotonin system in particular. “I wouldn’t say it’s slaying that theory forever,” Dr. Conley said, “but it’s definitely casting doubt.”

Another unexpected finding came in the context of relationships. Behavioral geneticists know that people tend to select life partners with similar DNA profiles in areas such as educational attainment. But in the new study, personality traits did not show much so-called “assortative mating” at all: In fact, personality variants among partners were matched mostly at random.

In contrast, spouses’ actual personalities — specifically their openness to experience — were sometimes correlated, perhaps because sharing daily life makes people more similar over time. Dr. Conley, who studies the interplay between genes and the environment, said that such hidden phenomena, scattered throughout the data set, are helpful for researchers like himself who are interested in understanding cause and effect.

“The next study that has double the sample size will find 3,000 variants, no surprise,” he said. “But the fact that we can now look into the dynamics between personality and marital stability, or personality and the labor market, or personality and the education system — that’s what makes this a really useful tool.”

Translation

科學家發現1,000多個與人格相關的基因變異（2/2）

超過一百萬個基因組幫助科學家辨識出與外向性、親和力、神經質等人格特質相關的DNA變異。研究人員測量了這些特質如何影響人們的生活方式

（繼續）

Tucker-Drob博士，一個在心理學上專注去研究人在思想、情感和行為上的差異， 叫 “個體差異” 的學術研究領域的人說: 「這確實是一個明顯的空白」。對他而言，人格不僅僅是一個抽象的概念：人們與自身和世界互動的方式會影響他們的收入、他們尋求的醫療保健類型，以及他們交友的倾向度。

他說：“個人性格與我認為社會上每一個人都會重視的各種實況都有密切相關。”

研究團隊掃描了基因組中約1,000萬個基因變異，以繪製「五大人格特質」圖譜。透過整合各種特質的不同研究，研究人員得以揭示人格傾向如何影響健康、習慣和生活方式的選擇。

例如，研究人員發現了258種與外向性相關的基因變異，比先前已知的變異數量增加了15倍。具有高度外向性的基因特徵似乎可以降低個體焦慮症、憂鬱症和創傷後壓力症候群的風險，這些疾病都涉及內化痛苦。但這種特徵也與過動症（ADHD）等神經發育障礙有關。

那些具有責任感（或稱為高效能和組織能力）的人似乎更有可能鍛鍊身體、選擇低熱量食物並擁有良好的睡眠。責任感的基因分數有助預測哪些人會在50歲時從市中心遷往富裕的郊區。

神經質被定義為一種情緒不穩定的傾向，它與10種不同的精神疾病、更高的體重指數，以及更高的吸煙率均有顯著相關性。研究參與者中，神經質基因評分較高的人似乎會即時地自我懷疑，經常在問卷中選擇「我不知道」之類的選項。

由於神經質可以作為精神疾病的強烈預測指標，一些研究人員對這些新發現如何揭示疾病的潛在誘因和途徑特別感興趣。普林斯頓大學的社會學家Dalton Conley並未有參與這項研究，但他對該研究結果挑戰心理學家長期以來所持有的一個理論 - 即神經質主要由血清素水平的差異所驅動 - 尤為感興趣。憂鬱症和焦慮症通常可以透過提高血清素水平的藥物來有效治療。

新的分析表明，神經質變異體確實在腦細胞中特別活躍 - 但並未揭示血清素系統有任何顯著差異。Conley博士說: “我不會說它會永遠徹底推翻那個理論”，“但它無疑提出了質疑。”

另一項出乎意料的發現來自人際關係領域。行為遺傳學家知道，人們傾向於選擇在教育程度等方面擁有相似DNA特徵的伴侶。但在這項新研究中，人格特質幾乎沒有表現出所謂的「同型交配」：事實上，伴侶之間的人格變異體大多是隨機匹配的。

相較之下，配偶的實際人格 - 特別是他們對新體驗的開放情度 - 有時卻存在相關性，這或許是因為共同的日常生活會隨著時間的推移使人們變得更加相似。研究基因與環境交互作用的Conley博士表示，這些散佈在資料集之中的各種隱藏現象，對於像他般致力於去理解因果關係的研究人員來說，是非常有幫助。

他說:「下一項樣本量翻倍的研究將會發現3,000個變異，這並不令人意外」 ，「但我們現在可以研究人格與婚姻穩定性、人格與勞動力市場、人格與教育體系之間的動態關係 - 這才是真正令它成為有用的工具」。

So, scientists have long known that personality is influenced by a number of factors — including DNA. The challenge has been deciphering the specific pathways through which a genetic blueprint influences the direction of a person’s life. Recently, a group of researchers find a symphony of 1,260 genetic markers that have ties to personality, nearly two-thirds of them are identified for the first time. Apparently, we can now look deeper into the dynamics between personality and marital stability, or personality and the labor market, or personality and the education system.

科學家發現1,000多個與人格相關的基因變異（1/2）

Recently The New York Times reported the following:

Scientists Find More Than 1,000 Genetic Variants Linked to Personality (1/2)

More than one million genomes helped identify DNA variants linked to extroversion, agreeableness, neuroticism and more. Researchers measured how those traits influenced how people lived.

The NYT - By Emily Baumgaertner Nunn (Emily Baumgaertner Nunn is a national health reporter for The Times, focusing on public health issues that primarily affect vulnerable communities.)

Sept. 3, 2026

Are you naturally anxious? Highly adventurous? More argumentative than you’d like to admit?

Those tendencies are often measured through what psychologists call the “Big Five” dimensions of personality: extroversion, agreeableness, conscientiousness, neuroticism and openness to experience. Each trait exists on a continuum and tends to remain fairly stable throughout adult life.

But what determines where you land on those spectra? Scientists have long known that personality is influenced by a host of factors — including DNA. The challenge has been deciphering the specific pathways through which a genetic blueprint nudges the direction of a person’s life.

To map this sprawling architecture, a group of experts formed a research consortium and analyzed more than one million genomes, searching for variants associated with personality. The researchers also compared the genes of thousands of siblings and parent-child pairs to rule out other factors that could be at play. With data from 46 different study cohorts, they found a symphony of 1,260 genetic markers tied to personality, nearly two-thirds of them identified for the first time.

The findings, published on Wednesday in the journal Nature, reaffirmed scientists’ understanding that temperament and disposition are shaped not by a few particular genes, but by thousands of tiny variants that can be expressed in different circumstances. The sheer scale of the project also brought new statistical power to the study of personality genetics, giving researchers a tool kit to investigate the biological mechanisms behind how we think, feel and behave.

“I view the 1,260 variants as kind of a testament to the fact that we’ve now got the power to answer all of these other questions that we couldn’t answer before,” said Elliot Tucker-Drob, a professor of psychology at the University of Texas at Austin and a leader of the study.

Common genetic differences identified in this study still account for only about 5 to 10 percent of personality variation among people. But experts caution against thinking about personality drivers as a pie chart, divided into neat percentages of genes versus environment. In reality, a person’s DNA and context are constantly interacting; experiences are the very tool that genetic predispositions use to mold who a person becomes.

In studies of genetic influence on educational attainment, much of what appears driven by DNA often turns out to be parental privilege or home environment in disguise. With personality, however, family comparison studies that looked for such confounding variables revealed that about 96 percent of the genetic influence indeed came directly from the DNA itself. That makes intuitive sense: Growing up in the same household might give siblings similar launching pads, but it almost never gives them similar temperaments.

Wednesday’s publication is, in some ways, a revitalization. In the late 20th century — the era of classical twin studies — personality was a central focus of behavioral genetics. But over the last decade, personality genetics has not been studied with nearly the intensity that other traits have, such as the risk of developing schizophrenia, in part because most personality traits were not considered medically relevant.

(to be continued)

科學家發現1,000多個與人格相關的基因變異（1/2）

超過一百萬個基因組幫助科學家辨識出與外向性、宜人性、神經質等人格特質相關的DNA變異。研究人員測量了這些特質如何影響人們的生活方式

你天生焦慮嗎？你充滿冒險精神嗎？你比自己願意承認的更愛爭辯嗎？

這些傾向通常透過心理學家所說的「五大人格特質」來衡量：外向性、宜人性、盡責性、神經質和開放性。每一種特質都存在於一個連續光譜上，並且在成年生活中往往保持相對穩定。

但是，是什麼決定了你在這些特質譜上的位置呢？科學家早已知道，人格受多種因素影響，包括DNA。真正的挑戰在於，如何解讀基因藍圖如何影響人的一生。

為了繪製出這套龐大的基因圖譜，一群專家組成了一個研究聯盟，分析了超過一百萬個基因組，尋找與人格相關的基因變異。研究人員還比較了數千對兄弟姐妹和親子對的基因，以排除其他可能的影響因素。他們利用來自46個不同研究隊列的數據，發現了1,260個與人格相關的基因標記，其中近三分之二是首次被發現。

這項研究成果於週三發表在《自然》雜誌上，再次印證了科學家們的認知：人的氣質和性格並非由少數特定基因決定，而是由數千個微小的基因變異共同帶來作用的結果，這些變異會在不同的情況下表達出來。該計劃的龐大規模也為性格遺傳學研究帶來了新的統計力，為研究人員提供了一套工具，用於探索我們思考、感受和行為背後的生物學機制。

德克薩斯大學奧斯汀分校心理學教授、該研究的負責人之一Elliot Tucker-Drob說道:「我認為這1,260個變異體證明了我們現在有能力回答以前無法回答的所有問題」。

這項研究中發現的常見基因差異仍只佔人格差異的5%到10%。但專家提醒，不要把性格驅動因素看成一個圓餅圖，簡單地劃分成基因和環境的百分比。事實上，一個人的DNA和環境因素一直在相互作用；個人經歷正是基因傾向塑造一個人性格的工具。

在關於基因對教育成就影響的研究中，許多看似由DNA驅動的因素，最終往往被證明是父母的優勢或家庭環境所變相驅動的。然而，在人格方面，針對此類混雜變數的家庭比較研究表明，約96%的遺傳影響確實直接來自DNA本身。這符合直覺：在同一個家庭中成長，或許能為兄弟姊妹提供相似的起點，但幾乎不可能讓他們擁有相似的個性。

週三發表的論文在某種程度上是對人格研究的復興。在20世紀後期 - 經典雙胞胎研究的時代 - 人格是行為遺傳學的核心研究方向。但在過去十年中，人格遺傳學的研究強度遠不及其他性格特徵，例如罹患精神分裂症的風險，部分原因是大多數的個人格特質被認為是無醫學上的關連。

（待續）

每年48萬美元的藥丸反映癌症藥物價格的新常態（1/2）

Recently The New York Times reported the following:

A $480,000-a-Year Pill Reflects a New Normal for Cancer Drugs (1/2)

Rasonque, the new pancreatic cancer treatment from Revolution Medicines, illustrates the huge inflation in cancer drug prices over the past two decades.

The NYT - By Rebecca Robbins (Rebecca Robbins is a Times reporter covering the pharmaceutical industry. She has been reporting on health and medicine since 2015.)

Aug. 31, 2026, 5:03 a.m. ET

Revolution Medicines set a sticker price of about $480,000 a year, or $663 a tablet, for its new pancreatic cancer drug — a cost that would have once been unthinkably high.

Today, such prices are routine for cancer drugs.

One cutting-edge CAR-T therapy now goes for $600,000 for a one-time infusion. A competitor, given the same way, is listed at $550,000. A daily pill for gastrointestinal cancer has a sticker price of $520,000 a year. A twice-daily pill for leukemia? It’s $430,000 a year.

In 2024 alone, nine cancer drugs were approved and then introduced with sticker prices above $400,000 annually, according to a tally by the Institute for Clinical and Economic Review, which evaluates the value of medicines.

That these prices have become commonplace would have been hard to imagine two decades ago, when even the prospect of a $100,000-a-year cancer drug evoked fierce criticism.

But since then, cancer drug prices have steadily increased, with few constraints beyond what a company thinks the market will bear. The expense is borne by government programs like Medicare, employers, patients and Americans who pay taxes and health insurance premiums.

A spokesman for Revolution Medicines, Brian Crawford, said the price of its new drug, Rasonque, “reflects its differentiation and the meaningful benefit it provides for patients.”

As is typical with other cancer drugs, the vast majority of the cost of Rasonque is expected to be covered through insurance, with varying out-of-pocket costs for patients. Mr. Crawford said uninsured and underinsured patients who met certain financial and medical criteria would receive the drug for free. The drug, also known as daraxonrasib, is taken as two pills a day.

In the medical world, much of the anger over cancer drug prices has been directed at pricey medicines that either failed or did not undergo clinical trials assessing whether they extend lives. Those drugs won approval because they could shrink tumors or delay their growth.

Revolution Medicines’ drug is not a cure, but it has shown that it can prolong life expectancy. In a key clinical trial, patients with advanced pancreatic cancer who got the pill lived for a median of 13.2 months, compared with 6.7 months for those who got chemotherapy.

Those results have electrified pancreatic cancer specialists and patients because they occurred in people who had no good treatment options and little time left to live.

In that context, it’s hard to say whether Revolution Medicines’ price is fair, said Stacie Dusetzina, a health policy professor at Vanderbilt University who studies drug pricing. “This drug does have substantial clinical benefits over existing treatment, which isn’t always the case for high-priced cancer drugs,” she said.

Cancer patients often stay on a drug for only a matter of months, stopping because it has become too toxic or their cancer has progressed. For example, in the clinical trial that won approval for Rasonque, patients were on the drug for a median of six months. But even over several months, the costs can pile up, and some patients who respond well can stay on a cancer drug for years.

Over the years, the public and lawmakers have expressed outrage at the high costs of insulin and drugs for H.I.V., hepatitis C and, most recently, obesity. One-time therapies for rare genetic diseases now routinely carry price tags of a few million dollars.

But cancer holds a unique place in the system, because care and drugs are so expensive and affect so many people.

For the past five years, employers have said cancer is the top disease category driving their medical expenses, according to a survey published in late August by the Business Group on Health, which represents large employers that provide health insurance to their workers.

Compounding the rising costs is that in some cancers, like multiple myeloma, patients are now routinely given three or four therapies at once.

The high prices aren’t limited to drugs that treat small numbers of patients. Oncology’s biggest blockbuster is Keytruda, which has a sticker price of $213,000 a year. It is given as an infusion or an injection every few weeks and has been used to treat several million patients.

For many older drugs, generic competition and government negotiations have sharply driven down costs. But there are hardly any limits on manufacturers’ ability to set high prices for newly approved medications.

“We allow pharmaceutical companies to charge whatever they want, and without any clear rationale, other than how much they think they can get,” said Dr. Aaron Kesselheim, a professor of medicine at Harvard and Brigham and Women’s Hospital who studies drug pricing.

(to be continued)

Translation

每年48萬美元的藥丸反映癌症藥物價格的新常態（1/2）

Revolution Medicines公司推出的新型胰臟癌治療藥物Rasonque，凸顯了過去二十年來癌症藥物價格的巨額上漲

Revolution Medicines公司為其新型胰臟癌藥物設定的標價約為每年48萬美元，即每片663美元 - 這在過去是難以想像的高昂價格。

如今，這樣的價格已成為癌症藥物的常態。

有一種尖端的CAR-T療法，一次性注入的費用就高達60萬美元。同樣的藥物，競爭對手的定價為 55 萬美元。一種治療胃腸道癌症的每日服藥，每年的價格高達 52 萬美元。一種治療白血病的每日兩次服藥呢？每年的標價為 43 萬美元。

根據評估藥物價值的臨床與經濟評估研究所 (ICER) 統計，光是 2024 年，就有九種癌症藥物獲準上市，其標價均超過每年 40 萬美元。

二十年前是難以想像的高昂價格如今已司空見慣。那時，即使是每年 10 萬美元的癌症藥物都會引發激烈的批評。

但自那時開始，癌症藥物的價格一直在穩步上漲，除了製藥公司認為市場能夠負擔的價格之外，幾乎沒有其他限制。最終，這筆費用由政府計劃如Medicare (聯邦醫療保險）、雇主、病患以及繳稅和醫療保險費的美國民眾承擔。

Revolution Medicines公司的發言人Brian Crawford表示，其新藥Rasonque的定價「體現了該藥的獨特性及其為患者帶來的顯著益處」。

與其他癌症藥物一樣，Rasonque的大部分費用預計將由保險覆蓋，患者只需自付一部分費用。Crawford先生表示，符合特定經濟和醫療條件的無保險或保險不足的患者將免費獲得該藥。該藥也稱為daraxonrasib，每日服用兩片。

在醫學界，人們對癌症藥物價格的憤怒大多集中在那些價格昂貴但療效不佳，或未經過臨床試驗評估是否能延長患者壽命的藥物。這些藥物之所以獲批，是因為它們能夠縮小腫瘤或延緩腫瘤生長。

Revolution Medicines公司的這款藥物並非治癒癌症的藥物，但已證明它可以延長患者的預期壽命。在一項關鍵的臨床試驗中，接受口服藥物治療的晚期胰臟癌患者的中位存活期為13.2個月，而接受化療的患者中位存活期僅為6.7個月。

這些結果令胰臟癌專家和患者都感到振奮，因為這些患者先前幾乎沒有有效的治療選擇，生命所剩無幾。

Vanderbilt大學研究藥物定價的衛生政策教授Stacie Dusetzina表示，在這種情況下，很難判斷Revolution Medicines公司的定價是否合理。 她說:「這種藥物確實比現有療法具有顯著的臨床效益，而高價抗癌藥物並非總是有明顯效益的」。

癌症患者通常只能服用一種藥物幾個月，就會因為藥物毒性過大或癌症擴展而停藥。例如，在為Rasonque贏得批准的臨床試驗中，患者的中位用藥時間為六個月。但即使只有幾個月，費用也會累積起來，一些有療效顯著的患者可以服用抗癌藥物數年之久。

多年來，公眾和立法者一直對胰島素以及治療愛滋病、丙型肝炎和最近肥胖症的藥物的高昂費用表示憤慨。如今，罕見遺傳疾病的一次性治療費用通常高達數百萬美元。

但癌症在醫療體系中佔有特殊的地位，因為癌症的治療和藥物費用極為昂貴，而且影響著許多人。

根據代表為員工提供醫療保險的大型雇主的「商業健康集團」（Business Group on Health）8月下旬發佈的一項調查，過去五年，雇主表示癌症是推高其醫療支出的首要疾病類別。

雪上加霜的是，對於某些癌症，例如多發性骨髓瘤，患者現在通常需要同時接受三到四種療法。

高昂的價格並非僅限於治療患者人數較少的藥物。腫瘤科最暢銷的藥物是Keytruda，年定價高達21. 3萬美元。該藥每隔幾週透過輸液或註射給藥，已用於治療數百萬名患者。

對於許多舊藥而言對於許多，，仿製藥的競爭和政府的談判已大幅降低了價格。但對於新核准的藥物，藥廠幾乎不受任何限制地設定高價。

哈佛大學和布萊根婦女醫院研究藥品定價的醫學教授Aaron Kesselheim博士說:「我們允許製藥公司隨意定價是沒有任何明確的理由，除了他們認為這藥能夠賺到多少」。

（待續）