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This Woman Feels No Pain. Decoding Her DNA Could Bring Relief to Millions.
Jo Cameron is a 75-year-old Scottish woman who has gone through life without experiencing significant pain of any kind. Even major surgery and childbirth failed to deliver the discomfort most of us would experience.
According to an interview with the BBC in 2019, Cameron only knows her skin is burning if she smells or sees it. To her, suffering is nothing more than an abstract concept.
The quirk that Cameron was born with is shared with just a few other people in the world. Called congenital analgesia, it is a one-in-a-million condition with multiple genetic causes that may come with other symptoms, such as sweating more or having no sense of smell.
Scientists at University College London (UCL) are now studying her genes to understand how pain pathways might be turned off in those with chronic conditions.
Pain is obviously a useful barometer for damage to the body. And yet sometimes the signal can get stuck in an overactive state that is no longer beneficial. When it lasts more than a few months, it's referred to as chronic pain. Cameron's genes could hold secrets to snapping out of the suffering.
"By understanding precisely what is happening at a molecular level, we can start to understand the biology involved and that opens up possibilities for drug discovery that could one day have far-reaching positive impacts for patients," says UCL pain geneticist James Cox.
Cameron's condition is caused by a rare variation in the FAAH-OUT gene, which was found and named in 2019 by Cox and his colleagues at UCL. It was uncovered in a part of the human genome historically thought to hold only 'junk' DNA that doesn't do anything useful.
How wrong that assumption was. As it turns out, FAAH-OUT plays a key role in modulating another gene, called FAAH (fatty acid amide hydrolase). This gene is sometimes called the 'happy gene' or 'forgetful' gene because it tends to make people less anxious and more absentminded.
You know that surge of adrenaline you get in a fearful situation? Cameron's FAAH-OUT mutation – in combination with another, more common variant in a nearby gene – means she doesn't even experience those feelings in a car crash.
In the past two decades, drug researchers have tried many times to make a drug that targets FAAH, and yet none has passed human clinical trials.
Understanding the interplay between FAAH and FAAH-OUT could help refine that effort – and lead to new understandings of pain.
The two genes are often co-expressed in the same cells, Cox and colleagues found in their latest study. Further experiments to mimic Cameron's condition revealed when FAAH-OUT was silenced or edited out of lab-grown human cells, the expression of FAAH was also reduced.
This, in turn, had an impact on genes encoding pain and opioid receptors, lipids that play a role in wound healing, and brain proteins that modulate mood, the researchers have found.
"The FAAH-OUT gene is just one small corner of a vast continent, which this study has begun to map," says molecular biologist Andrei Okorokov from UCL.
"As well as the molecular basis for painlessness, these explorations have identified molecular pathways affecting wound healing and mood, all influenced by the FAAH-OUT mutation.
"As scientists, it is our duty to explore and I think these findings will have important implications for areas of research such as wound healing, depression, and more."
Not until she was 65 years old did Cameron realize just how different her experience of life was to most other humans.
Now, the hope is that the unique secrets of her cells could provide a happier and less painful existence to many more.
注释：
quirk: n
表示"怪癖；急转"，means "a strange attitude or habit;a narrow groove beside a beading"，如：The most annoying quirk of his is wearing a cap all the time. 他最令人感到厌恶的怪癖就是无论何时都戴著帽子。In other words, the ordering of the DNA code wasn't a quirk of nature. 换句话说，DNA的有序编码不是大自然的随性之作。
congenital analgesia: 表示"先天性无痛症"
congenital：adj
表示"天生的；先天的"， means "present at birth but not necessarily hereditary"，如：The congenital form is spread to the fetus through the bloodstream.先天的形式是通过血液传播给胎儿。
analgesia: n
表示" 痛觉缺失"， means "absence of the sense of pain without loss of consciousness"，如：It indicates that Shixuan decoction has a better analgesia effect. 提示十宣汤具较好的镇痛效果。
barometer: n
表示"晴雨表; 气压计；"，means "instrument for measuring the pressure of the atmosphere,used to get information about the weather,etc."，如：Hair is a barometer of your general health. 头发是你基本健康状况的晴雨表。Air pressure is measured by a barometer. 空气压力用气压计度量。
snap: v
表示" 猛咬; 劈啪作响；砰然关上；"，means "snatch with the teeth; (cause sth to) to break suddenly/open/close sth with a sharp noise"，如：The shark snapped its jaws shut.鲨鱼啪嗒一声把嘴合上了。The violin string snapped because it was fastened too tight.小提琴的弦上得太紧，突然断了。A sharp, snapping sound, such as the report of a firearm. 爆裂声尖锐的爆裂声(如枪击声)
genome: n
表示" 基因组；染色体组"，means "the full DNA sequence of an organism;"，如：Scientists have decoded the dog genome. 科学家已经译解了狗的基因组。
modulate: v
表示" 调整；调节（声音"，means "fix or adjust the time, amount, degree, or rate of; change the key of, in music"，如：The speaker had a really noble voice which he could modulate with great skill.这位演说者有副相当好的嗓子，他能很技巧地调整它。
amide: n
表示" 酰胺；氨基化合物"，means "any organic compound containing the group -CONH2"，如：Trial and error revealed that it was best to put in the amide before the epoxide. 尝试和误差法表明，最好在环氧化之前引进酰胺基。
hydrolase: n
表示" [生化]水解酶"，如：Lipase is a kind of widely used hydrolase.脂肪酶是一种广泛应用的水解酶。
Absentminded: adj
表示" 心不在焉的；茫然的；恍惚的"，means "lost in thought; showing preoccupation"，如：Michael looked at her in an absentminded fashion.迈克尔望着她，表现出心不在焉的样子。
adrenaline: n
表示"肾上腺素(使激动兴奋等)"，means "a catecholamine secreted by the adrenal medulla in response to stress (trade name Adrenalin); stimulates autonomic nerve action"，如：He felt a surge of pure adrenaline as he won the race.他赢得比赛时感到一阵激动。
mutation: n
表示"突变；变异"，means "a change or alteration in form or qualities"，如：Our teacher has mutation of sounds suddenly.我们的老师突然语音发生了变化。
Interplay: n
表示" 相互影响"，means "reciprocal action and reaction"，如：The story of our lives is the interplay of the bucket and the dipper.我们的生活里充满了桶和舀水杯的交织。
Opioid: n
表示"类鸦片"，如：Opioid dependence is a chronic, repeated relapsing disease in brain. 类鸦片依赖是一种慢性、反复发作性脑疾病。
receptor：n
表示"受体；接受器"，means "a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response"，如：Placebo effect tied to brain receptor activity. 安慰剂的效果与大脑内受体活动度有关。
lipid: n
表示" 脂质；油脂"，如：The blood plasma lipid examination was abnormal.血浆脂质出现不同程度的异常变化。
中文简要说明：
现年75岁，住在苏格兰的的乔•卡梅隆 (Jo Cameron)， 是一位极罕见的「无痛者」，对她来说，疼痛是一种抽象的感觉，即使遭遇大手术，或是生孩子，她也不需要任何止痛药。除此之外，她的伤口康复能力颇佳，现在科学家正在研究她的DNA，试图找到关闭痛觉的方法。
科学警报(SciencAalert)报导，根据 2019 年 BBC 的一场采访，卡梅隆有一次遇到一场煮饭时不慎烧到手，竟然是闻到烧焦味才知道自己的皮肤在燃烧。对她来说，痛苦不过是一个抽象的概念。
她「超能力」是在她 60 多岁时才被发现的，当时她接受了两次髋关节手术，医护人员建议她吃止痛药，但她坚称说自己没事，才被医学界发现她没有痛感。这个案例极为罕见，被称为「先天性痛觉不敏感」( congenital analgesia)，源自于基因突变，大约2万5千名新生儿才有一例，但卡梅隆又是其中最特别的一种，她受伤后的康复能力相当好，没有因为感觉不到伤口而一直发炎。
她同意医学界以她为研究对象，以了解疼痛感觉可以如何关闭，现在伦敦大学医学院 (UCL) 的科学家似乎找到了线索。
科学家发现，卡梅隆身上的FAAH-OUT 基因发生罕见变异，该基因是在2019年发现并命名，并没引起什么关注，因为这么多年来，找不到该基因的用处，因此人们认为FAAH-OUT只是没有任何用处的「垃圾DNA」。
然而， FAAH-OUT 在调节另一个名为 FAAH(脂肪酸酰胺水解酶)的基因，起了关键作用。FAAH基因有时被称为「快乐基因」或「健忘基因」，因为它会使人们不那么焦虑，而且容易心不在焉。
卡梅隆的 FAAH-OUT基因突变之后，有348个基因被抑制，其中包括与疼痛传导有关的工作；另有797个基因被活化，现已知有一些与伤口复原相关。总而言之，这些可能有助于解释卡梅隆对疼痛的不敏感、明显的伤口愈合速度提升，以及她不会感到焦虑和恐惧的原因。
其实，FAAH的基因很早就被科学家发现与疼痛有关，在过去的二十年里，研究人员多次尝试制造针对FAAH的药物，但是忽略了该基因也有自己的控制器，也就是FAAH-OUT。
现在了解 FAAH 和 FAAH-OUT 之间的相互作用后，或许可以帮助科学家重新理解疼痛的基因成因。
这项研究很可能开发出不会上瘾的止痛药，甚至可以发现加速伤口愈合、治疗抑郁症等研究的关键。
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