用藥風險，男性女性大不相同The Drug-Dose Gender Gap By RONI CARYN RABIN

健康

用藥風險，男性女性大不相同

RONI CARYN RABIN 報道 2013年02月25日

Ellen Weinstein

大部分安眠藥的目的是讓你安睡八小時。近來，美國食品與藥品管理局（Food and Drug Administration，簡稱FDA）的研究者對一種用於治療半夜醒來的短效安眠藥進行評估，則是希望了解患者在次日早上醒來時，體內還殘餘着多少藥物。
結果在血液檢測中研究者發現了性別造成的差異：男性在代謝這種名為酒石酸唑吡坦(Intermezzo)的藥物時，速度比女性更快。最終FDA在批准該葯時，規定男性使用劑量為3.5毫克，女性為1.75毫克。

酒石酸唑吡坦中的有效成分為唑吡坦，它被用於其他多種助眠藥物中，其中包括了安必恩(Ambien)。但直至本月，FDA才規定將安必恩的女性服用劑量減半。
安眠藥絕對不是唯一有可能給女性帶來意想不到的、甚或是危險副作用的藥物。此前有幾項研究表明，女性在使用從阿司匹林(aspirin)到麻醉劑的多種藥物時，所出現的反應都不同於男性。研究者現在剛剛開始理解到該問題的廣度。有不少人相信正因為如此，女性在服藥後會發生過高比例的副反應，而且這些副作用往往非常嚴重。
“這不僅跟安必恩有關——它只揭示了冰山一角，”美國國家衛生研究所(National Institutes of Health)女性健康研究辦公室主任簡寧·克萊頓博士(Janine Clayton)這樣表示。“很多葯的效果都存在着性別差異，其中一些已經為人們熟知，但也有些還未被充分認識到。”
在1993年以前，育齡女性通常都不得參與各類新葯人體試驗。而在這一年，當FDA取消了禁令後，該機構的研究人員注意到，由於沒有女性參加有關阿司匹林對心臟病和腦卒中治療的里程碑式的研究，科學界對“阿司匹林對治療患該類疾病的女性是否真的有效存有疑慮。”
由於大量藥物的測試人群大多或全部為男性，科學家要等到藥物上市後，才有可能了解其對女性的副作用。美國政府問責局(Government Accountability Office)的一項調查發現，從1997年到2000年間被強制下架的10種藥物中，有八種對女性會構成更大的健康風險。
舉例來說，抗組胺葯特非那定(Seldane)和胃腸道葯西沙必利(Propulsid)在引發可能致命的心律不齊問題時，女性發病的機率都要比男性更高。克萊頓博士介紹說，目前仍在銷售的大量藥物所引發的心律不齊，在女性身上都表現得更為頻繁，其中包括抗生素、抗精神病葯、治療瘧疾藥物和降膽固醇藥物。女性服用的葯也往往比男性多。
藥效的性別差異表現在兩方面。一些葯，比如治療高血壓的維拉帕米(Verapamil)和抗生素紅霉素，看來對女性的療效更明顯。而在另一方面，據女性健康研究協會(Society for Women's Health Research)表示，相比男性，女性更容易在麻醉術中途蘇醒，也更有可能遭受麻醉劑導致的副作用。
研究還發現，酒精、香煙和可卡因對女性產生的作用與男性不同。
這不僅是因為女性的身材通常矮小一點。女性的體脂率較高，而且荷爾蒙波動大，每月出現月經周期，因此代謝藥物也會有所不同。韋斯利·林塞(Wesley Lindsey)是奧本大學(Auburn University)藥學院的助理教授，與人合著了一篇關於藥效性別差異的論文，他說：“一些藥物是更加偏於水溶性，往往會在血液中駐留；而另一些葯更可能在脂肪組織中駐留。”
“如果藥物是脂溶性的，”——也就是說被脂肪細胞吸收——“它就會由這些組織器官吸收，停留在體內的時間更長，”林塞博士進一步說，“身體無法快速將它代謝，你會發現這種葯的藥力更持久。”
在肝臟代謝、腎功能和某些特定的消化酶方面也存在着性別差異。口服避孕藥、更年期和絕經期激素療法使得女性用藥的問題顯得更為複雜。喬治城大學(Georgetown)健康、老化與疾病之性別差異研究中心的主管凱瑟琳·桑德伯格(Kathryn Sandberg)舉例說，比如一些研究認為在雌激素水平較低時，女性可能需要服用更高劑量的血管緊張素受體阻滯劑以降低血壓，因為這時她們體內的蛋白質含量升高，會導致血管收縮。
很多研究者認為，應當在新葯研發之初——甚至是在開展人體藥物試驗開始前，就收集藥效性別差異的數據。
桑德伯格博士說：“通往新葯的路徑始於最基礎的科學——你先要研究動物的疾病模式，就此發現藥物靶點。但現在有九成的科研人員仍然只研究雄性動物的疾病模式。”
在這方面已經出現了改進。在接受採訪時，FDA藥品評估和研究中心的羅伯特·坦普爾(Robert Temple)博士說，該機構於1993年制訂了新指南，要求在藥品研發的最早期階段就要開始注意研究藥效性別差異，同時也要分性別來解讀臨床實驗數據。
他說，有一種治療腸易激綜合症的葯叫阿洛司瓊（alosetron，商品名“羅腸欣”），對該葯的早期研究時顯示它對男性效果不顯著。因此在臨床試驗時只招募了女性志願者，在審批通過時也註明只能供女性患者服用。（由於存在嚴重副作用，現在該葯被限制銷售。）
也有些科學家認為，藥物代謝試驗只有10到15個志願者參加，規模太小，不足以發現藥效性別差異。根據近期的一項分析，就算現在參加臨床試驗的女性比以往多了，但在治療心臟病和腎臟病、甚至是癌症的臨床試驗中，參與的女性仍然較少。
林塞博士說：“現在有個大問題，那就是我們並不能確切地知道，性別會帶來多大的差異。我們對此實在知之甚少。”

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本文最初出版於2013年1月29日。
翻譯：Noey

The Drug-Dose Gender Gap

By RONI CARYN RABIN February 25, 2013 

 

Most sleeping pills are designed to knock you out for eight hours. When the Food and Drug Administration was evaluating a new short-acting pill for people to take when they wake up in the middle of the night, agency scientists wanted to know how much of the drug would still be in users' systems come morning.
Blood tests uncovered a gender gap: Men metabolized the drug, Intermezzo, faster than women. Ultimately the F.D.A. approved a 3.5 milligram pill for men, and a 1.75 milligram pill for women.

The active ingredient in Intermezzo, zolpidem, is used in many other sleeping aids, including Ambien. But it wasn't until earlier this month that the F.D.A. reduced doses of Ambien for women by half.

Sleeping pills are hardly the only medications that may have unexpected, even dangerous, effects in women. Studies have shown that women respond differently than men to many drugs, from aspirin to anesthesia. Researchers are only beginning to understand the scope of the issue, but many believe that as a result, women experience a disproportionate share of adverse, often more severe, side effects.

"This is not just about Ambien - that's just the tip of the iceberg," said Dr. Janine Clayton, director for the Office of Research on Women's Health at the National Institutes of Health. "There are a lot of sex differences for a lot of drugs, some of which are well known and some that are not well recognized."
Until 1993, women of childbearing age were routinely excluded from trials of new drugs. When the F.D.A. lifted the ban that year, agency researchers noted that because landmark studies on aspirin in heart disease and stroke had not included women, the scientific community was left "with doubts about whether aspirin was, in fact, effective in women for these indications."
Because so many drugs were tested mostly or exclusively in men, scientists may know little of their effects on women until they reach the market. A Government Accountability Office study found that 8 of 10 drugs removed from the market from 1997 through 2000 posed greater health risks to women.
For example, Seldane, an antihistamine, and the gastrointestinal drug Propulsid both triggered a potentially fatal heart arrhythmia more often in women than in men. Many drugs still on the market cause this arrhythmia more often in women, including antibiotics, antipsychotics, anti-malarial drugs and cholesterol-lowering drugs, Dr. Clayton said. Women also tend to use more medications than men.
The sex differences cut both ways. Some drugs, like the high blood pressure drug Verapamil and the antibiotic erythromycin, appear to be more effective in women. On the other hand, women tend to wake up from anesthesia faster than men and are more likely to experience side effects from anesthetic drugs, according to the Society for Women's Health Research.
Women also react differently to alcohol, tobacco and cocaine, studies have found.
It's not just because women tend to be smaller than men. Women metabolize drugs differently because they have a higher percentage of body fat and experience hormonal fluctuations and the monthly menstrual cycle. "Some drugs are more water-based and like to hang out in the blood, and some like to hang out in the fat tissue," said Wesley Lindsey, assistant professor of pharmacy practice at Auburn University, who is a co-author of a paper on sex-based differences in drug activity.
"If the drug is lipophilic" - attracted to fat cells - "it will move into those tissues and hang around for longer," Dr. Lindsey added. "The body won't clear it as quickly, and you'll see effects longer."
There are also sex differences in liver metabolism, kidney function and certain gastric enzymes. Oral contraceptives, menopause and post-menopausal hormone treatment further complicate the picture. Some studies suggest, for example, that when estrogen levels are low, women may need higher doses of drugs called angiotensin receptor blockers to lower blood pressure, because they have higher levels of proteins that cause the blood vessels to constrict, said Kathryn Sandberg, director of the Center for the Study of Sex Differences in Health, Aging and Disease at Georgetown.
Many researchers say data on these sex differences must be gathered at the very beginning of a drug's development - even before trials on human subjects begin.
"The path to a new drug starts with the basic science - you study an animal model of the disease, and that's where you discover a drug target," Dr. Sandberg said. "But 90 percent of researchers are still studying male animal models of the disease."
There have been improvements. In an interview, Dr. Robert Temple, with the Center for Drug Evaluation and Research at the F.D.A., said the agency's new guidelines in 1993 called for studies of sex differences at the earliest stages of drug development, as well as for analysis of clinical trial data by sex.
He said early research on an irritable bowel syndrome drug, alosetron (Lotronex), suggested it would not be effective in men. As a result, only women were included in clinical trials, and it was approved only for women. (Its use is restricted now because of serious side effects.)
But some scientists say drug metabolism studies with only 10 or 15 subjects are too small to pick up sex differences. Even though more women participate in clinical trials than in the past, they are still underrepresented in trials for heart and kidney disease, according to one recent analysis, and even in cancer trials.
"The big problem is we're not quite sure how much difference this makes," Dr. Lindsey said. "We just don't have a good handle on it."

Readers may submit comments or questions for The Consumer by e-mail to consumer@nytimes.com.

 

Picasso’s Masterpieces Made With House Paint

 

 

Observatory

Picasso’s Masterpieces Made With House Paint

DOUGLAS QUENQUA February 23, 2013 

Scientists using a high-energy X-ray instrument say they have solved the long-running debate over what kind of paint Picasso used in his masterpieces.It was common house paint, said Volker Rose, a physicist at the Argonne National Laboratory who led the study, published in Applied Physics A: Materials Science & Processing.

 

“We were looking into pigments taken from Picasso’s white paint, which from a material perspective is zinc oxide, and we were able to study the impurities that are there,” Dr. Rose said.
The scientists also bought samples of decades-old house paint on eBay. After comparing those samples with Picasso’s paint, they determined that the two shared the same chemical makeup.
The instrument was a hard X-ray nanoprobe, developed by the Department of Energy to give scientists a close-up view of the chemical elements in physical materials. Its intended use is to improve the production of high-performance materials and energies. Using the nanoprobe, the researchers could view particles of paint that were just 30 nanometers wide. (A typical sheet of paper is 100,000 nanometers thick.)
In his regular work, Dr. Volker uses the nanoprobe to study zinc oxide, a key ingredient in batteries, energy-saving windows and liquid-crystal displays for computers and television. Because zinc oxide exists in white paint as well, it made a valuable clue for the physicist to learn about Picasso’s paint.
Some art historians have long held that Picasso was among the first major artists to switch from traditional artists’ paint to house paint, which is more affordable and creates a glossy image without brush strokes.

畢加索傳世名畫系建築塗料所作

DOUGLAS QUENQUA 報道 2013年02月23日

Chris Gash

科學家稱，他們使用一種高能X射線儀解決了一個長期爭執不下的問題：畢加索的傳世名畫中採用的是哪種顏料？
美國阿貢國家實驗室(Argonne National Laboratory)的物理學家沃爾克·羅斯(Volker Rose)的答案是：普通建築塗料。他主持的相關研究發表在期刊《應用物理學A卷：材料科學與工藝》(Applied Physics A: Materials Science & Processing)上。

羅斯博士說，“我們研究了畢加索採用的白色顏料粉末。從材料學角度看，就是氧化鋅。而且我們也研究了其中含有的雜質。”
科學家們還從eBay上購買了幾十年前生產的建築塗料樣品。他們把這些樣品與畢加索的顏料進行對比，判定兩者的化學組分相同。
科學家採用的儀器是一台硬X射線納米探測儀。這種儀器由美國能源部(Department of Energy)研發，以使科學家能細緻地觀察物理材料的化學成分，從而促進高性能材料及能源的生產。使用這種納米探測儀，研究者可以觀察粒徑僅為30納米 的顏料顆粒。（一張普通的紙的厚度是10萬納米。）
羅斯博士在日常工作中使用這種儀器研究氧化鋅。氧化鋅是電池、節能窗及電腦和電視液晶顯示器的關鍵原料。它也存在於白色顏料中，因而為羅斯博士了解畢加索的顏料提供了寶貴線索。
長期以來，一些藝術史學家認為，畢加索是從傳統顏料轉向建築塗料的首批重要藝術家之一。建築塗料更平價，作畫光滑流暢，毫無畫筆的痕迹。

翻譯：梁英

Mice Fall Short as Test Subjects for Humans’ Deadly Ills

Evan McGlinn for The New York Times

Dr. H. Shaw Warren is one of the authors of a new study that questions the use of laboratory mice as models for all human diseases.

By GINA KOLATA

Published: February 11, 2013 143 Comments

For decades, mice have been the species of choice in the study of human diseases. But now, researchers report evidence that the mouse model has been totally misleading for at least three major killers — sepsis, burns and trauma. As a result, years and billions of dollars have been wasted following false leads, they say.

音節

sep • sis

発音

sépsis

[名]（複 -ses 〔-siz〕）[U]《病理学》敗血症.

The study’s findings do not mean that mice are useless models for all human diseases. But, its authors said, they do raise troubling questions about diseases like the ones in the study that involve the immune system, including cancer and heart disease.

“Our article raises at least the possibility that a parallel situation may be present,” said Dr. H. Shaw Warren, a sepsis researcher at Massachusetts General Hospital and a lead author of the new study.

The paper, published Monday in Proceedings of the National Academy of Sciences, helps explain why every one of nearly 150 drugs tested at a huge expense in patients with sepsis has failed. The drug tests all were based on studies in mice. And mice, it turns out, can have something that looks like sepsis in humans, but is very different from the condition in humans.

Medical experts not associated with the study said that the findings should change the course of research worldwide for a deadly and frustrating condition. Sepsis, a potentially deadly reaction that occurs as the body tries to fight an infection, afflicts 750,000 patients a year in the United States, kills one-fourth to one-half of them, and costs the nation $17 billion a year. It is the leading cause of death in intensive-care units.

“This is a game changer,” said Dr. Mitchell Fink, a sepsis expert at the University of California, Los Angeles, of the new study.

“It’s amazing,” said Dr. Richard Wenzel, a former chairman at the department of internal medicine at Virginia Commonwealth University and a former editor of The New England Journal of Medicine. “They are absolutely right on.”

Potentially deadly immune responses occur when a person’s immune system overreacts to what it perceives as danger signals, including toxic molecules from bacteria, viruses, fungi, or proteins released from cells damaged by trauma or burns, said Dr. Clifford S. Deutschman, who directs sepsis research at the University of Pennsylvania and was not part of the study.

The ramped-up immune system releases its own proteins in such overwhelming amounts that capillaries begin to leak. The leak becomes excessive, and serum seeps out of the tiny blood vessels. Blood pressure falls, and vital organs do not get enough blood. Despite efforts, doctors and nurses in an intensive-care unit or an emergency room may be unable to keep up with the leaks, stop the infection or halt the tissue damage. Vital organs eventually fail.

The new study, which took 10 years and involved 39 researchers from across the country, began by studying white blood cells from hundreds of patients with severe burns, trauma or sepsis to see what genes were being used by white blood cells when responding to these danger signals.

The researchers found some interesting patterns and accumulated a large, rigorously collected data set that should help move the field forward, said Ronald W. Davis, a genomics expert at Stanford University and a lead author of the new paper. Some patterns seemed to predict who would survive and who would end up in intensive care, clinging to life and, often, dying.

The group had tried to publish its findings in several papers. One objection, Dr. Davis said, was that the researchers had not shown the same gene response had happened in mice.

“They were so used to doing mouse studies that they thought that was how you validate things,” he said. “They are so ingrained in trying to cure mice that they forget we are trying to cure humans.”

“That started us thinking,” he continued. “Is it the same in the mouse or not?”

The group decided to look, expecting to find some similarities. But when the data were analyzed, there were none at all.

“We were kind of blown away,” Dr. Davis said.

The drug failures became clear. For example, often in mice, a gene would be used, while in humans, the comparable gene would be suppressed. A drug that worked in mice by disabling that gene could make the response even more deadly in humans.

Even more surprising, Dr. Warren said, was that different conditions in mice — burns, trauma, sepsis — did not fit the same pattern. Each condition used different groups of genes. In humans, though, similar genes were used in all three conditions. That means, Dr. Warren said, that if researchers can find a drug that works for one of those conditions in people, it might work for all three.

The study’s investigators tried for more than a year to publish their paper, which showed that there was no relationship between the genetic responses of mice and those of humans. They submitted it to the publications Science and Nature, hoping to reach a wide audience. It was rejected from both.

Science and Nature said it was their policy not to comment on the fate of a rejected paper, or whether it had even been submitted to them. But, Ginger Pinholster of Science said, the journal accepts only about 7 percent of the nearly 13,000 papers submitted each year, so it is not uncommon for a paper to make the rounds.

Still, Dr. Davis said, reviewers did not point out scientific errors. Instead, he said, “the most common response was, ‘It has to be wrong. I don’t know why it is wrong, but it has to be wrong.’ ”

The investigators turned to Proceedings of the National Academy of Sciences. As a member of the academy, Dr. Davis could suggest reviewers for his paper, and he proposed researchers who he thought would give the work a fair hearing. “If they don’t like it, I want to know why,” he said. They recommended publication, and the editorial board of the journal, which independently assesses papers, agreed.

Some researchers, reading the paper now, say they are as astonished as the researchers were when they saw the data.

“When I read the paper, I was stunned by just how bad the mouse data are,” Dr. Fink said. “It’s really amazing — no correlation at all. These data are so persuasive and so robust that I think funding agencies are going to take note.” Until now, he said, “to get funding, you had to propose experiments using the mouse model.”

Yet there was always one major clue that mice might not really mimic humans in this regard: it is very hard to kill a mouse with a bacterial infection. Mice need a million times more bacteria in their blood than what would kill a person.

“Mice can eat garbage and food that is lying around and is rotten,” Dr. Davis said. “Humans can’t do that. We are too sensitive.”

Researchers said that if they could figure out why mice were so resistant, they might be able to use that discovery to find something to make people resistant.

“This is a very important paper,” said Dr. Richard Hotchkiss, a sepsis researcher at Washington University who was not involved in the study. “It argues strongly — go to the patients. Get their cells. Get their tissues whenever you can. Get cells from airways.”

“To understand sepsis, you have to go to the patients,” he said.

This article has been revised to reflect the following correction:
Correction: February 11, 2013

An earlier version of this article misstated the position of Dr. Richard Wenzel. He is a former chairman of the department of internal medicine at Virginia Commonwealth University. He is not currently the chairman.

Domestic cats killing, 一隻佛羅里達家貓的320公里回家路

 

James Morton

Those Cute and Cuddly Killing Machines

By NATALIE ANGIER 3:05 PM ET

Domestic cats kill billions of birds and mammals a year, a new report shows, many more than previous estimates.

• I.H.T. Rendezvous: Economist Wants to Rid New Zealand of Cats

 

 

一隻佛羅里達家貓的320公里回家路

PAM BELLUCK 報道 2013年01月31日

Barbara P. Fernandez for The New York Times

里克特夫婦，70歲的雅各布（左）和63歲的邦尼，以及他們的三色貓霍利。霍利跋涉了320公里回家。

沒人知道這事兒是怎麼發生的：在一次家庭旅行中走失的一隻家養母貓，終於在兩個月後，從近200英里（約合320公里）遠的地方返回了她的家鄉。
就連科學家對這隻貓是怎麼回來的都迷惑不解。4歲的三色貓霍利(Holly)去年11月初與雅各布·里克特(Jacob Richter)和邦尼·里克特(Bonnie Richter)夫婦在佛羅里達州的代托納比奇參加房車聚會時走失；新年前夜她出現在離西棕櫚灘里克特家不到1英里的一個後院，四肢不穩，而且虛弱、憔 悴。

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英國布里斯託大學人類動物學研究所(University of Bristol's Anthrozoology Institute)所長約翰·布拉德肖(John Bradshaw)問道，“你肯定是同一隻貓？”因為在其他一些案例中，他懷疑“其實不過是流浪貓，但是人們有一種心理辯護，希望是同一隻貓”。
不過，霍利不僅有毛皮上獨特的黑棕色小丑圖案，而且還有植入的芯片可以確定她的身份。
美國科羅拉多大學(University of Colorado)的行為生態學家馬克·貝科夫(Marc Bekoff)說，“我真的相信這些故事，不過他們實在是很難解釋。也許靠街頭機靈，也許會讀動物線索，或是會認車，或因為其好獵手的本性。我沒有這方面的數據。”
實際上，關於貓如何導航，科學上沒有定論。人們更仔細研究的遷徙動物，比如鳥類、龜類和昆蟲等，利用磁場、嗅覺線索，或太陽定方向。
科學家說，狗回家的事情更常聽到，儘管也很少見。布拉德肖說，這可能表明，狗有從狼身上遺傳下來的用磁場線索導航的能力。
布拉德肖還說，貓在熟悉環境中有很好的導航能力，它們能靠視覺和氣味記住地點，並且能輕易地找到捷徑。
雖然陌生、遙遠的地方對貓來說似乎會有問題，但是他和英國劍橋大學(Cambridge University)的行為生物學家帕特里克·貝特森(Patrick Bateson)都說，貓可以嗅到長距離的氣味。貝特森說，“我們可以假設，它們能夠將北風與松樹的味道聯繫起來，於是會向南行。”
紐約動物行為學家彼得·博爾歇特(Peter Borchelt)猜測，霍利可能靠視覺或聲音沿着佛羅里達海岸和95號州際公路(Interstate 95)而行，還決定“保持自己的右邊是公路，左邊是大海”。
但他說，“沒人會做個實驗，把一群貓帶到四面八方的各個地點，然後看看哪些貓能回到家裡。”
英國研究貓的生物學家羅傑·泰伯(Roger Tabor)說，與那個試驗最接近的，也許是德國在1954年進行的一項研究。在該研究中，貓被放在一個有頂的圓形迷宮中，迷宮每隔15度就有一個出口， 大部分貓都在朝家的方向走出了迷宮，但如果它們的家與迷宮之間的距離少於五公里，則那麼做的可靠率更高。
但有過一些貓出人意料地找到了家的事兒。
“這事的確在我身邊發生過，”傑克遜·加里克斯(Jackson Galaxy)說，他是動物行為研究者，也是動物星球(Animal Planet)《管教惡貓》(My Cat From Hell)節目的主持。他住在科羅拉多州博爾德時，曾從小鎮的一頭搬到另一頭，搬家後不久，他養的那隻家貓逃走了，十天後，這隻貓出現在以前的房子前， “它在一個從前從未去過的地區走了五英里（約八公里），”加里克斯說。
泰伯提到幾個他認為可信的、涉及更長距離的故事，比如，1989年，俄羅斯的一隻三色貓，從主人的母親在沃羅涅什的家，回到了主人在莫斯科的家，走 的距離約為325英里；1997年，一隻名為忍者的貓，在主人從猶他州的法明頓搬到華盛頓州的米爾克里克一年後，回到了法明頓；1978年，澳大利亞的一 家人因度假，將室內生活的波斯貓託付給親戚，這隻貓從那裡逃走，最終回到1000英里之外的主人家。
泰伯還說，英國黑諾特利村(Black Notley)有一隻暹羅貓，多次跳上火車，然後在白諾特利站下來，走回幾英里之外的黑諾特利。
然而，要解釋這些貓的旅行並不像區分黑白那麼容易。
就佛羅里達州這件事來說，小貓的爪子提供了一些線索，幫助我們透過迷霧看到一點事實真相。雖然布拉德肖曾猜測，霍利可能在路上搭了便車，也許她藏在了一輛沿着I-95公路南行的卡車車蓬下面，但是，霍利的爪子卻說明，她不是整個旅程都了搭車，而且行程對她來說並不輕鬆。
“當時她的爪墊在流血，”里克特女士說，“她的爪子已經磨成很奇怪的樣子。她前面的爪子變得非常尖，而後面的爪子則幾乎磨的快沒有了。”
科學家稱，這正與遠距離行走相符合，因為後爪提供推進力，而前爪則主要從事比如撕東西等行為。里克特夫婦還說，霍利的體重從13.5磅下降到7磅。
霍利看上去根本不像一個愛冒險的流浪者，雖然她的出身可能給她提供了基因上的優勢。里克特女士說，霍利的生母是一隻流浪貓，在里克特家的房車停放區 里閑逛，而霍利出生在某個人家的空調機里。六個星期大小的時候，霍利走進他們的停車棚，跳上里克特母親的大腿，當時“她的肚子上還有空調機打開時被劃而留 下的傷疤”，里克特女士說。
科學家表示，這些早期經歷過於短暫，不足以解釋霍利可能適應野外的原因，畢竟，除了偶爾跑出去追蜥蜴，大部分時間霍利都在室內生活。但是這也許意味着霍利具有一些天性，比如敏捷和堅韌。
貝科夫說，“真有各種不同的性格。有的魚膽小，有的魚膽大；似乎也有膽小和膽大的蜘蛛。至於這隻貓，可以說，她有對付生活中各種困難的性格。”
貝科夫說，室內養的貓，其求生行為並不會完全喪失，比如抓老鼠，或者知道太陽的方向。
里克特夫婦——63歲的退休護士邦尼和70歲的退休航空機械監管員、頗有成就的投球手雅各布——在去年才開始帶着霍利旅行，而她很容易就能適應了旅館、棚屋，或者房車。
但是，在代托納比奇好山姆房車聚會(Good Sam R.V. Rally)期間，里克特一家和另外3000個房車家庭一起，在一個靠近高速公路的地方露營，一天晚上，當里克特女士的母親打開門時，霍利一下沖了出去。 第二天的煙火可能進一步讓她受了驚，經過幾天的尋找，還通知了動物機構，貼了告示，但還是沒有找到貓，里克特夫婦只好回了家。
兩星期後，一個動物救助人員曾打電話給里克特夫婦，說在貓頭鷹連鎖餐廳代托納比奇店的後面看到一隻很像霍利的貓在吃東西，該店的員工會把食物放在那裡喂流浪貓。
後來，在新年前夜，52歲的大學行政助理巴布·馬佐拉(Barb Mazzola)在其西棕櫚灘家的後院里發現了一隻“幾乎站不起來”的貓，她連發出喵喵的叫聲都很吃力。在接下來的六天里，馬佐拉和她的孩子們悉心照料這 隻貓，把吃的東西放到院子里，包括專門給貓喝的奶，最終，這隻貓進了馬佐拉的房子。
他們給她起名珂賽特，珂賽特是《悲慘世界》里的孤兒，還帶她去看了 Paws2Help（一家私立動物福利機構——譯註）的獸醫，薩拉·貝格(Sara Beg)。貝格說，這隻貓的體重偏輕並嚴重脫水，“後爪和爪床嚴重磨損，很可能是長期在柏油路上行走所致，”但是“精神狀態很好，也很機警”，沒被寄生 蟲、心絲蟲或病毒感染。貝格說，“她多慮，對身邊她不認識的人有些害怕，所以我認為她沒有主動接近人，搭了便車。我覺得她是自己一路走回來的。”
馬佐拉說，“我差點不想問”機構的工作人員，“因為我想留下這隻貓，但是我還是說，‘查一下，搞清楚她身上有沒有芯片。’”當被告訴這隻貓身上有芯片時，她說，“我當時就哭了。”
里克特夫婦看到霍利時也哭了，而當被放到里克特先生肩膀上時，霍利一下子就放鬆了。霍利回家後很順利，但是她回家的歷程仍然是個謎。
加里克斯說，“它們怎麼做到這些，我們一點概念也沒有。如果有人說他知道，那是在說謊。如果你找到了答案，看在上帝的份上，請告訴我是什麼。”

本文最初發表於2013年1月20日。
翻譯：谷菁璐、黃錚、陳亦亭

A Cat’s 200-Mile Trek Home Leaves Scientists Guessing

By PAM BELLUCK January 31, 2013

Barbara P. Fernandez for The New York Times

Jacob Richter, 70, left, and Bonnie Richter, 63, flank Holly, the cat that traveled 190 miles to find her way home.

Nobody knows how it happened: an indoor housecat who got lost on a family excursion managing, after two months and about 200 miles, to return to her hometown.
Even scientists are baffled by how Holly, a 4-year-old tortoiseshell who in early November became separated from Jacob and Bonnie Richter at an R.V. rally in Daytona Beach, Fla., appeared on New Year's Eve - staggering, weak and emaciated - in a backyard about a mile from the Richters' house in West Palm Beach.

"Are you sure it's the same cat?" wondered John Bradshaw, director of the University of Bristol's Anthrozoology Institute. In other cases, he has suspected, "the cats are just strays, and the people have got kind of a mental justification for expecting it to be the same cat."
But Holly not only had distinctive black-and-brown harlequin patterns on her fur, but also an implanted microchip to identify her.
"I really believe these stories, but they're just hard to explain," said Marc Bekoff, a behavioral ecologist at the University of Colorado. "Maybe being street-smart, maybe reading animal cues, maybe being able to read cars, maybe being a good hunter. I have no data for this."
There is, in fact, little scientific dogma on cat navigation. Migratory animals like birds, turtles and insects have been studied more closely, and use magnetic fields, olfactory cues, or orientation by the sun.
Scientists say it is more common, although still rare, to hear of dogs returning home, perhaps suggesting, Dr. Bradshaw said, that they have inherited wolves' ability to navigate using magnetic clues.
Cats navigate well around familiar landscapes, memorizing locations by sight and smell, and easily figuring out shortcuts, Dr. Bradshaw said.
Strange, faraway locations would seem problematic, although he and Patrick Bateson, a behavioral biologist at Cambridge University, say that cats can sense smells across long distances. "Let's say they associate the smell of pine with wind coming from the north, so they move in a southerly direction," Dr. Bateson said.
Peter Borchelt, a New York animal behaviorist, wondered if Holly followed the Florida coast by sight or sound, tracking Interstate 95 and deciding to "keep that to the right and keep the ocean to the left."
But, he said, "nobody's going to do an experiment and take a bunch of cats in different directions and see which ones get home."
The closest, said Roger Tabor, a British cat biologist, may have been a 1954 study in Germany which cats placed in a covered circular maze with exits every 15 degrees most often exited in the direction of their homes, but more reliably if their homes were less than five kilometers away.
But there have been other cats who made unexpected comebacks.
"It's actually happened to me," said Jackson Galaxy, a cat behaviorist who hosts "My Cat From Hell" on Animal Planet. While living in Boulder, Colo., he moved across town, whereupon his indoor cat, Rabbi, fled and appeared 10 days later at the previous house, "walking five miles through an area he had never been before," Mr. Galaxy said.
Professor Tabor cited longer-distance reports he considered credible: Murka, a tortoiseshell in Russia, traveling about 325 miles home to Moscow from her owner's mother's house in Voronezh in 1989; Ninja, who returned to Farmington, Utah, in 1997, a year after her family moved from there to Mill Creek, Wash.; and Howie, an indoor Persian cat in Australia who in 1978 ran away from relatives his vacationing family left him with and eventually traveled 1,000 miles to his family's home.
Professor Tabor also said a Siamese in the English village of Black Notley repeatedly hopped a train, disembarked at White Notley, and walked several miles back to Black Notley.
Still, explaining such journeys is not black and white.
In the Florida case, one glimpse through the factual fog comes on the little cat's feet. While Dr. Bradshaw speculated Holly might have gotten a lift, perhaps sneaking under the hood of a truck heading down I-95, her paws suggest she was not driven all the way, nor did Holly go lightly.
"Her pads on her feet were bleeding," Ms. Richter said. "Her claws are worn weird. The front ones are really sharp, the back ones worn down to nothing."
Scientists say that is consistent with a long walk, since back feet provide propulsion, while front claws engage in activities like tearing. The Richters also said Holly had gone from 13.5 to 7 pounds.
Holly hardly seemed an adventurous wanderer, though her background might have given her a genetic advantage. Her mother was a feral cat roaming the Richters' mobile home park, and Holly was born inside somebody's air-conditioner, Ms. Richter said. When, at about six weeks old, Holly padded into their carport and jumped into the lap of Mr. Richter's mother, there were "scars on her belly from when the air conditioner was turned on," Ms. Richter said.
Scientists say that such early experience was too brief to explain how Holly might have been comfortable in the wild - after all, she spent most of her life as an indoor cat, except for occasionally running outside to chase lizards. But it might imply innate personality traits like nimbleness or toughness.
"You've got these real variations in temperament," Dr. Bekoff said. "Fish can by shy or bold; there seem to be shy and bold spiders. This cat, it could be she has the personality of a survivor."
He said being an indoor cat would not extinguish survivalist behaviors, like hunting mice or being aware of the sun's orientation.
The Richters - Bonnie, 63, a retired nurse, and Jacob, 70, a retired airline mechanics' supervisor and accomplished bowler - began traveling with Holly only last year, and she easily tolerated a hotel, a cabin or the R.V.
But during the Good Sam R.V. Rally in Daytona, when they were camping near the speedway with 3,000 other motor homes, Holly bolted when Ms. Richter's mother opened the door one night. Fireworks the next day may have further spooked her, and, after searching for days, alerting animal agencies and posting fliers, the Richters returned home catless.
Two weeks later, an animal rescue worker called the Richters to say a cat resembling Holly had been spotted eating behind the Daytona franchise of Hooters, where employees put out food for feral cats.
Then, on New Year's Eve, Barb Mazzola, a 52-year-old university executive assistant, noticed a cat "barely standing" in her backyard in West Palm Beach, struggling even to meow. Over six days, Ms. Mazzola and her children cared for the cat, putting out food, including special milk for cats, and eventually the cat came inside.
They named her Cosette after the orphan in Les Misérables, and took her to a veterinarian, Dr. Sara Beg at Paws2Help. Dr. Beg said the cat was underweight and dehydrated, had "back claws and nail beds worn down, probably from all that walking on pavement," but was "bright and alert" and had no parasites, heartworm or viruses. "She was hesitant and scared around people she didn't know, so I don't think she went up to people and got a lift," Dr. Beg said. "I think she made the journey on her own."
At Paws2Help, Ms. Mazzola said, "I almost didn't want to ask, because I wanted to keep her, but I said, 'Just check and make sure she doesn't have a microchip.'" When told the cat did, "I just cried."
The Richters cried, too upon seeing Holly, who instantly relaxed when placed on Mr. Richter's shoulder. Re-entry is proceeding well, but the mystery persists.
"We haven't the slightest idea how they do this," Mr. Galaxy said. "Anybody who says they do is lying, and, if you find it, please God, tell me what it is."