事件记录
面试官: 大象很少得癌症. 一项新的研究或许可以解释其中的原因.
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面试官: 我正在和医生谈话. Schiffman, 亨茨曼癌症研究所的儿科肿瘤学家, 犹他大学医学院和初级儿童医院. Dr. 希夫曼，这是个很棒的故事. 在大发娱乐开始之前，你能解释一下你的发现吗?
Dr. Schiffman: 好吧, 大发娱乐所能展示的是大象, 尽管它们体型庞大, 体型是人的100倍，寿命超过50-60岁, 几乎很少会得癌症. 这是令人惊讶的，因为如此多的细胞在如此长的时间内分裂, 你可能会认为几乎每头大象都会在很小的时候患上癌症. What we were able to show was that elephants may be protected from developing cancer due to extra copies of genes called p53 that protect us from cancer.
面试官: 因此，这可能会对开发新疗法产生影响?
Dr. Schiffman: We know that if we're missing working copies of these genes that there is an increased risk of cancer. 事实上，大发娱乐知道一半的人类癌症都没有正常工作的p53. 另一方面，大象的p53是人类的20倍. 大发娱乐认为这就是他们不患癌症的原因. Now what we're trying to do in the laboratory is figure out how do we mimic this effect of these extra copies of p53.
面试官: 我喜欢这个想法，你基本上是跟随自然的引导. 大自然已经想出了解决办法. 大发娱乐只需要弄清楚它做了什么.
Dr. Schiffman: What we're trying to do in the laboratory here at the University of Utah is take a page out of nature's playbook. 就像你说的，大自然已经决定了. What we want to do is learn from that and see how do we apply this to children and adults who already have cancer or maybe at a genetically high risk to develop cancer.
面试官: 我想知道的一件事是，你说大象真的会得癌症. 但是大发娱乐真的知道吗? 我是说，有没有可能没人能找到它?
Dr. Schiffman: 大发娱乐研究了644头大象的死亡记录, 主要来自圈养的大象, 试图找出他们的死因. 大发娱乐发现的是大发娱乐观察的644头大象的癌症导致的死亡, 低于5%. So 4.8%的大象死亡可能是由于癌症. 在人类中，癌症的估计死亡率为11%至25%.
面试官: 实际上大象并不是唯一很少得癌症的大型动物. 你分析了很多动物
Dr. Schiffman: 大发娱乐查看了圣地亚哥动物园维护的数据库. 你会认为那些活得更久的动物, 它们有更多的细胞质量, 他们患癌症的风险也会增加. 因为细胞越多, 细胞分裂的时间越长, 仅仅是偶然, the opportunity to accumulate mutations and eventually transform into cancer would be present. 但大发娱乐发现，实际上，两者之间并没有关系. 如果有什么区别的话, 像大象这样的大型动物, 像狮子, 比如驼鹿等等, 它们似乎对癌症有轻微的保护作用.
所以大发娱乐认为大自然已经进化到保护不同的物种免受癌症的侵害, 这样它们才能长得更大, 这样他们就能活得很长. We believe as we expand our studies and we look further that every different animal that is protected from cancer will have evolved a slightly different way of avoiding cancer or becoming cancer resistant. 这是进化医学学习的概念, what we can from nature around us is very exciting and we think holds great promise for treating our human patients.
面试官: 那么这到底是怎么开始的呢? 我是说，不像实验室的科学家每天都和大象打交道.
Dr. Schiffman: 几年前，我参加了一个讨论癌症进化的会议. 还有一位演讲者, 卡洛Maley, 来自亚利桑那州立大学, 是在描述一种叫做皮托悖论的现象吗, which is the observation that large animals like elephants develop much less cancer than you'd expect by chance alone. Carlo went on to describe that he had looked at the genome of African elephants in his laboratory and there 他们 found that these elephants seem to have extra copies of this p53 gene.
I went up to Carlo after the talk and was discussing that in our lab at the University of Utah, we take care of patients and study patients who have something known as Li-Fraumeni syndrome, 哪些人缺少p53的有效拷贝. And we said wouldn't it be wonderful to try to get elephant blood to try to compare that elephant blood from elephants that don't get cancer with patients that seem to get an awful lot of cancer, 有时是90-100%的癌症风险?
It was a few weeks later that I happened to be at the zoo with my children watching the elephants. 好吧, 他们接着说，在霍格尔动物园，每周有一次, 他们 draw blood from these African elephants to make sure that 他们're healthy and their hormones are in balance. 嗯，一个电灯泡马上就熄灭了. It took several months of paperwork and scientific an ethical review from the Hogle Zoo. 但从那时起, I'm pleased to say that our clinical study coordinators go directly down to the whole Hogle Zoo where 他们 receive the blood and we rush it back to the laboratory and that's where we've done our experiments.
面试官: 大象的血告诉了你什么?
Dr. Schiffman: 当大发娱乐观察大象细胞对放射或化疗的反应时, DNA破坏因子通常由于突变导致癌症. 大发娱乐发现大象的细胞非常敏感. 几乎所有的大象细胞都处于高度戒备状态, 大发娱乐认为是因为这些额外的p53拷贝. 当这些大象细胞暴露在这些DNA破坏剂中, 它们几乎立即发生细胞凋亡, 哪个是细胞死亡还是细胞自杀. 这就好像大象在说：“大发娱乐不患癌症是非常重要的. We need to not try to fix the cells but let's just kill them and start over from scratch."
面试官: 这与人类细胞的反应相比如何?
Dr. Schiffman: We were able to look and compare to our patients with this Li-Fraumeni syndrome and show that their cells actually don't die that frequently in response to DNA damaging agents. 它们继续分裂，继续这些突变, 大发娱乐认为是什么导致了他们患癌症的风险增加. 但是大象细胞, 比Li-Fraumeni患者细胞或人类对照细胞要高得多, 他们, 再一次。, 所有的细胞都会死亡或凋亡.
面试官: So even healthy human cells don't go through as much self destruction or apoptosis says the elephant cells do?
Dr. Schiffman: 这是正确的. 事实上，三分之一到一半的人会在一生中患上癌症. 所以在人类细胞中确实存在一些p53触发的细胞凋亡. 但它不如大象细胞凋亡好. The elephant apoptosis is more than twice the amount of the humans and we think that seems to be enough to protect these elephants from developing cancer.
面试官: 这是你所期望的吗, 我的意思是, 这些细胞会自我消灭而不是, 我不知道, 试着解决这个问题?
Dr. Schiffman: 这完全出乎大发娱乐的意料. 大发娱乐原以为大象的细胞会很快修复. But we were shocked to see that the elephant cells were repairing the DNA damage at about the same rate as the human cells. It was only when we looked at the measurement of cell death that we noticed the big difference.
面试官: So you know all of this is based on the fact that elephants have these extra copies of p53 - 40 of them compared to 2 in people. 他们是怎么弄到这么多副本的?
Dr. Schiffman: 是的，这是个很好的问题. 当大发娱乐仔细观察这些额外拷贝的序列时, what we discovered along with our research collaborators was that these extra copies appear to be what's called retro genes. This means that these genes have been reinserted throughout evolutionary time back into the elephant genome. So throughout the past 55 million years as the elephant developed into a large animal with a long life span, we think the reason it was able to do so was because these extra retro genes were reinserted into the elephant genome.
The other thing that we were able to show in the paper is if you take an elephant retro gene and you put it into a human cell, 所以大发娱乐使用了人类细胞系, 大发娱乐能够看到一些迹象表明这些复古基因, these elephant genes can actually be active in a human cell and trigger some of the same responses in the same genes to be involved as we see with normal p53. This is very exciting because it opens up the door as a potential therapeutic using these elephant genes in humans.
面试官: 那么接下来你要做什么呢?
Dr. Schiffman: What we want to be able to do is try to figure out can we actually develop a drug or approach to help these children that we care for, that other people are caring for children in hospitals all across the country and adults as well? Is there a novel way that we can discover to use this information to try to treat these cancers?
播音员: 有趣，内容丰富，而且都是为了更好的健康. 大发娱乐是Scope健康科学广播.