They look like tiny bacteria, have been implicated in several diseases and have even been hailed as a completely overlooked branch of the tree of life. But are 'nanobacteria' genuinely alive? New research suggests that the answer is probably no.
Ever since they were first described in the early 1980s, nanobacteria — which can be just 50 nanometres, or millionths of a millimetre, across — have captured the imagination of everyone from health experts to space biologists. A panel convened in 1998 by the US National Academy of Sciences concluded that the particles are too small to be alive, but that didn't stop people from being fascinated by them, and some companies even say that they can detect nanobacterial infections.
Some scientists have argued nanobacteria could be the source of life on Earth.But now the nanobacteria theory has taken a blow. New research suggests that, besides being too small to be alive, they may also be made of something not much more complex than simple chalk.
Death knell?
Jan Martel of Taiwan's Chang Gung University and John Young of Rockefeller University in New York created particles that look exactly like nanobacteria by incubating human serum with the chemical ingredients of simple calcium carbonate, or limestone.
The researchers then compared their creations with naturally occurring 'nanobacteria-like particles' from human blood samples. The particles not only looked identical to the limestone mix, they also showed no traces of DNA or RNA. The researchers then blasted the particles with enough radiation to slaughter any bacteria, and found that the particles still looked the same.
"I am pretty confident this will put an end to the biotic mechanism for nanobacteria," says Young, who reported the research in Proceedings of the National Academy of Sciences 1.
But why were some biologists so eager to believe that these were genuine life forms? Because the particles grow in such a life-like way, says Young. They even split in two in a way that resembles dividing bacteria. "They seem to grow, to propagate, and divide — you would swear they are a biological organism — but they're not," he says.
What is most intriguing about nanobacteria is that, although they seem to form by a chemical reaction between calcium and carbon dioxide — both of which are found naturally dissolved in blood — they are not simple lumps of chalk. "We believe what we have found is a complex of organic molecules and minerals," Young says.
That means that nanobacteria probably become coated with proteins or other organic molecules, which stop them from growing like a regular, jagged limestone crystal and instead look like round blobs.
It is these organic coatings that might have tricked experts into thinking that nanobacteria are alive, suggests John Cisar, a microbiologist at the US National Institutes of Health in Bethesda, Maryland. "But the simpler explanation is that they are not life forms," he says.
Commercial interest
Still, biological tests are commercially available for nanobacteria. One company, Nanobac Pharmaceuticals of Tampa, Florida, offers immunological tests to detect antibodies against nanobacteria, or 'calcifying nanoparticles', as it calls them, in human serum or plasma.
But when Martel and Young tested this product as part of their study, they found that the antibodies detected by the test also react with albumin, a protein widely found in blood serum. Young therefore suggests that many nanobacteria in the blood may be coated in albumin, and the test detected these.
Brady Millican, a representative of Nanobac, says "there are lots of rogue proteins associated with the structure itself". He says the test kit marketed by the company, which contains two different antibodies, is an assay that "captures more of the surface of the calcifying nanoparticle".
Young does believe, however, that nanobacteria can cause disease. Given the right chemical conditions, they "aggregate like crazy", he says. Perhaps this is a cause of extra-skeletal calcification, a painful and debilitating condition in which a kind of 'bone' forms in body areas such as tendons.
Cisar, on the other hand, thinks that although calcium carbonate deposits in the body can cause some ailments, nanobacteria are probably benign because they are so widespread in the body. "Every place you look for these things you find them," he says. "There's no particular pathology."
译文:
纳米细菌理论招来非议
它们看起来像是些微小的细菌。人们曾将它们与一些疾病联系在一起，并将它们称为生命之树上被完全忽略的一个分支。但“纳米细菌”是否真正存在呢？新的研究表明，这个问题的答案很可能是否定的。
从20世纪80年代初首次被人们描述至今，纳米细菌（其直径可能只有50纳米，或1毫米的百万分之一）已经激发起健康专家乃至宇航生物学家们的丰富想象。美国国家科学院于1998年成立的一个专家小组得出了这样的结论：这些微粒小得根本无法生存。然而这一结论丝毫没有妨碍人们对这些它们的迷恋，有些公司甚至声称他们能够检查出纳米细菌造成的感染。
一些科学家曾争辩说纳米细菌可能是地球生命的起源，但目前该纳米细菌理论却遭到了人们的质疑。新的研究工作表明，除纳米细菌“体积小得无法存活”的理由外，它们甚至可能是由一些比结构简单的白垩土复杂不了多少的物质构成的。
研究结果是否预示着纳米细菌理论的终结？
台湾长庚大学的简·马特尔和纽约洛克菲勒大学的约翰·杨通过将人类血清与简单碳酸钙或石灰石中的化学成分混在一起进行培养的方式制造出了外观极像纳米细菌的微粒。
研究者们随后又将他们培养出的物质与取自人类血样的自然形成的“看似纳米细菌的微粒”进行比较。这些微粒看上去既不与石灰石的混合物完全相同，也未表现出DNA或RNA存在的迹象。研究者们接下来又使用足量的射线照射这些微粒，确保彻底杀死其中的任何细菌，发现这些微粒与处理前无异。
约翰·杨说：“我非常自信这项实验将推翻有关纳米细菌具有生物机能的说法。”他还在美国国家科学院的学报上公布了该项研究的结果。
然而，为什么一些生物学家却急于相信这些微粒是实实在在的生命形态呢？约翰·杨认为原因是这些微粒能够像生命体那样生长。它们甚至可以像细菌分裂那样由一个分裂为两个。“看上去它们的确在生长、繁殖，在进行细胞分裂——由此你会断言它们是肯定是生物体——然而情况并不是这样。”他这样说道。
最让人好奇的是，尽管纳米细菌看似通过钙与二氧化碳（这两种物质均可在自然状态下溶于血）间的化学反应生成的，但它们并不是简单的白垩块。约翰·杨说：“我们相信我们所看到的是有机分子与矿物质的合成物。”
这意味着纳米细菌外面可能包裹着一层蛋白质或其它有机分子。这层物质使它们无法像普通的、外表凹凸不平的石灰石晶体那样逐渐增大，而是外表变得像个圆形块状物。
位于马里兰州贝塞斯达市的美国国家健康研究所的微生物学家约翰·西萨认为，可能正是这些有机的包裹层诱使专家们错误地认为“纳米细菌”是有生命的。“但更坦率的解释是它们根本就不是生命形态。”他这样说道。
商业利益
尽管如此，商业方面对纳米细菌的生物学试验仍在继续。佛罗里达州坦帕市的一家名为“纳米细菌制药”的公司进行了一项免疫学测试，目的是在人类血清或血浆中查找用来对抗纳米细菌（或该公司称之为的“钙化纳米微粒”）的抗体。
作为研究工作的一部分，当简·马特尔和约翰·杨对该合成物进行试验时，他们发现该项试验检测到的抗体也与清蛋白（一种普遍存在于血清中的蛋白质）发生反应。约翰·杨由此认为血液中的许多纳米细菌的表面可能也包有一层清蛋白。该项试验也的确检测到了一些这样的纳米细菌。
纳米细菌研究的代表人物布雷迪·梅里肯声称：“世界上存在着大量由其本身结构导致的劣等蛋白质。”他说该公司出售的含有两种不同抗体的试剂盒是一种“可以采集更多钙化纳米微粒的表面信息”的尝试。
然而，约翰·杨并不认为纳米细菌可以致病。他说，如果具备适当的化学条件，这些纳米细菌就发生“剧烈聚合”。这或许就是造成人体骨外钙化的原因。骨外钙化是一种痛苦且能够致人体虚的疾病。该病可造成在肌腱等人体部位形成一种“骨骼”。
另一方面，西萨则认为尽管体内的碳酸钙沉积可能导致某些疾病，但这并非纳米细菌的过错，原因是这些纳米细菌在体内的分布非常广泛。“在人体的任何地方你都可以找到这些纳米细菌。”他说，“它们之间并没有特别的病理学关联。”