A recent toast to James Watson highlights a tolerance for bigotry many want excised from the scientific community.
A potent carcinogen lurks within certain traditional Chinese medicines.
August 7, 2013|
WIKIMEDIA, BOGDANPlants of the Aristolochia genus have for centuries been used in Chinese herbal remedies, but they contain a naturally carcinogenic compound that causes mutations in the cells of people who consume them, according to two studies published in Science Translational Medicine today (August 7). The papers reveal that the compound, called aristolochic acid, causes more mutations than two of the best-known environmental carcinogens: tobacco smoke and UV light.
“A lot of people in the lay public assume that if something is herbal or natural that it is necessarily healthy,” said Marc Ladanyi, an investigator in the human oncology and pathogenesis program at Memorial Sloan-Kettering Cancer Center in New York who was not involved in the studies. “But this work very clearly shows that this natural plant product is extremely genotoxic and carcinogenic.”
Despite the long history of Aristolochia use in herbal remedies, evidence of the plants’ inherent danger emerged only recently. In the early 1990s, women who had received Aristolochia treatments at a weight loss clinic in Belgium developed kidney problems that progressed to renal failure and, in later years, to abnormal growths in their upper urinary tracts. More recently, Aristolochia contamination of local wheat crops was determined to be the cause of a high incidence of urothelial carcinomas of the upper urinary tract (UTUC) among rural communities on the banks of the Danube river in Europe. And in Taiwan, where recent prescription records reveal that approximately one-third of the population has taken Aristolochia-containing medicines, the incidence of UTUCs is the highest in the world.
Aristolochic acid has been banned in most countries since 2003. But, said Thomas Rosenquist of Stony Brook University in New York, “there are a lot of countries in Asia, like India, that still use it as part of their traditional herbal medicines. And even though it is banned in places like China, it is still readily available.”
The continued use of the plants might be because “[practitioners] may be slow to accept that they are actually hurting people that they are trying to help,” said Rosenquist. “And there may be a 20- to 30-year lag time between exposure to the carcinogen and [developing cancer], so making the connection might be difficult.”
In addition, many people may simply not know about the risk, said Steve Rozen of the Duke-National University of Singapore Graduate Medical School. “I’m eager to make sure this paper gets public press, because I think it’s important that people really understand the dangers.”
Rosenquist, Rozen, and their teams conducted two separate studies to analyze the genome-wide mutations in patients with UTUCs who had known exposure to aristolochic acid. The two reports found that an unusual mutation, called an A-to-T transversion, previously identified in aristolochic acid-exposed tissues, was abundant throughout the genomes of the cancerous cells. And the number of mutations in general was unusually high—far greater than that seen in lung cancers caused by smoking or in melanomas caused by UV exposure.
“The number of mutations identified per megabase of DNA was pretty astounding,” said Elaine Mardis, director of technology development at The Genome Institute at Washington University in St. Louis, who was not involved in the work. “Heretofore we thought that melanoma was the world class leader in terms of mutation number, or rate, but this now looks like it’s above and beyond that.”
The genome-wide analyses also revealed a preference for mutations to occur at particular sequence motifs—CAG or TAG—and to occur on the non-transcribed strand of coding DNA, indicating some mutations were erased as a result of transcription-coupled repair. These patterns, together with the extremely high mutation frequency and the abundance of A-to-T transversions, equated to a genomic signature of aristolochic acid exposure.
Identifying the signature in a patient’s DNA probably wouldn’t change the way they are treated, said Rosenquist. But screening for the signature in individuals thought to have been exposed to aristolochic acid may enable early detection of UTUCs. “We are trying to develop a screen to detect DNA carrying these mutations in plasma and urine . . . and see whether it has the sensitivity to detect those cancers before other routine methods [would],” he said.
In addition to the known risk of developing UTUC, Rozen’s team discovered that certain liver cancer genomes exhibited the telltale signature of aristolochic acid exposure. Thus, more organs might be at risk from exposure to the carcinogen than originally thought.
The sequencing of other cancer genomes will reveal whether this is indeed the case. For now though, perhaps the most important message of the two studies is that consuming these plants can certainly be dangerous. “As is often the case in cancer research, the biggest successes can be in prevention,” Rozen said.
M.L. Hoang et al., “Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing,” Science Translational Medicine, 5: 197ra102, 2013.
S.L. Poon et al., “Genome-wide mutational signatures of aristolochic acid and its application as a screening tool,” Science Translational Medicine, 5: 197ra101, 2013.
August 10, 2013
So... is there any evidence that indicated Chinese people who have been using these herbal remedies over the millenia were cursed with cancer?
August 10, 2013
Dionysius, if you google 'cancer rates in china', the article at the top of the list says "Cancer is the leading cause of death in Beijing". Over the years there have been reports of high incidence of specific cancers in population clusters throughout China.
August 12, 2013
1. If you are familliar with the Chinese culture (i.e. beyond the first article on google), you'll realise that the Chinese are fully aware of the potential side effects and toxicity of some of the ingredients used in traditional medicine. Maybe not for Aristolochia but they're perfectly familliar with the concept. In fact, many therapies were based on the idea of using more potent toxcins to "drive away" the weaker kinds. (I'm not saying that the idea is scientific, but they definitely know about it.)
2. Not many people turn to traditional medicine these days in China, especially not the younger generations. Therefore, even though cancer is the leading cause of death in many Chinese cities, it's unlikely that Aristolochia and the alike are responsible for such incidents.
3. As far as we know, Aristolochia only causes cancer in kidney, while the most common cancer in China is lung cancer, followed by stomach and liver cancers. Compared to the risk of inhaling polluted air filled with PM2.5, drinking toxic water and ingesting pesticides covered vegetables, the ingestion of Aristolochia poses almost minimum threat...
August 12, 2013
Dionysius & Intron: The sceince is there yet denial persists. This is why TCM is a religion more then a medicine. When evidence is presented that one TCM remedy works but another doesn't, the TCM believers deny it because it's in their 2 thousand year old book.
I don't care what is in your antequated books. If it doesn't stand up to modern standards of science, it's crap.
Time to get with this century and ditch the quackery.
August 12, 2013
The headline calls for panic, but the article says "Aristolochic acid has been banned in most countries since 2003". In other words, some people in China and India continue practices that are detrimental to their health - and that's not news.
The studies are important, and it is vital to study alternative medicine practices scientifically. (Which, btw, takes lots of money.) But dismissing a large spectrum of practices as "quackery" is no more insightful, practical or scientific.
August 12, 2013
It seems members of the "scientific" community just can't stop beating the dead horse of the dangers of aristolochia - an issue that has been discussed ad nauseum. aristalochia is an easy target - a simple topic - which can easily create fear and opposition against alternative medicines... for the benefit of... well, we can all easily follow that money trail.
Whether you personally think chinese herbology has merit, not, there are a couple of flaws that make this article the same kind of crap every aristalochia article is:
1) the dangers of aristalochia are VERY well known in asia. in fact, medicinals with aristalochia in it intended for internal usage have undergone extensive processing to remove virtually all of the aristalochic acid. This means that people aren't actually consuming the amounts of aristalochic acid taht this article implies. Why isn't this ever mentioned?
2) The belgian weightloss study, which used a chinese medicinal of the aristalochia family, seriously dropped the ball. For one thing, they used he wrong plant, because they couldn't be bothered to either get someone who reads chinese, or confirm the authenticity of the species. They ended up using a plant that is never used inernally, because of well known toxicity. For another thing, they didn't bother to process it to remove the toxicity, but used it raw. In other words, they couldn't be bothered to use traditional processing techniques that are strictly adhered to in asia when using this plant. Therefore, the pharmaceutical company that funded this study is solely responsible for all the unrelated deaths, because of their ineptitude. Why aren't we talking about that?
3) Aristalochic acid is banned in the US. So, what is this article warning us against? Don't go to china and get confused by the herbs you buy on the street corner - you might kill yourself? Thanks? Furthermore, you can still buy herbs form teh aristalochia family in the US, because they have been processed correctly - this means they have no aristalochic acid in them. Again, this points to the fact that it's not really a danger, and if it is, it's only a danger when pharmaceutical companies get their hands on it.
4) correlation does not equal causation. china and taiwan are some of the most polluted countries on earth, well known to deliberatly add toxic chemicals to food (melamine, plasticizer, etc). so, high rates of cancer really don't prove anything at all.
again, the issue is not whether you think chinese medicinals are efficacious, or not. the issue is that this is crap journalism and obviously biased. in this case, aristalochic plants are nothing more than a scape goat of bad pharmaceutical studies, an easy way to incense the public by creating another "threat", and a sure-fire way to get your name in some scientific journel. way to go guys.
August 13, 2013
I am sure TCM practioners are well aware of that. There are many human made substances which cause cancer. Why scientists do not focus on that.
August 14, 2013
This is not news. Aristolochia's carcinogenic effect and toxicity have been known for years by Chinese http://zh.wikipedia.org/zh/%E9%A9%AC%E5%85%9C%E9%93%83%E9%85%B8#cite_note-12
Go correct your misleading headline!
August 14, 2013
Articles like this don't often mention that aristolochic acid is an aromatic nitro compound, which is rather uncommon for a natural product. These compounds have what's called a structure alert for genotoxicity, because they are metabolised by animals to other compounds that react directly with DNA. Put simply, they can be classified as likely carcinogens just by looking at the chemical structure. We have to come to terms with the fact that living organisms engage in chemical warfare, and that many plants (probably the majority) are quite good at that, specially when the enemy is mammalian.
One difficulty in identifying aristolochic acid as a food contaminant was that at the low doses encountered for example in the Balkans the long latency for cancer made it hard to trace the cause. Research was aided by the fact that the cancer involved is not one of the most common types. We could hypothesise that people might be exposed to traces other carcinogens that would be less likely to be identified if they cause more than one common cancer.
If something with a structure alert is found as an impurity in a medicine, great care is taken to investigate it. If necessary, such impurities are eliminated or their concentrations are limited with wide safety margins. Likewise, alerting structures set off alarms during the evaluation of substances under chemical safety regulations such as REACH. One can understand that people who do these investigations get upset if products such as herbal medicines aren't even subject to adequate identification procedures.
The approach to impurities in medicines is in fact a little bit inconsistent, as some nitrofurans and related synthetic nitroaromatic antibiotics are still on the market for administration to humans, though they are banned for food animals because of carcinogenic residues (www.genotox.chrblee.net).
Finally, on the subject of natural products that look curiously unnatural, we could recall the amusing discovery a few decades ago of diazepam (valium; an organochlorine compound) in wheat and lormetazepam in potato. Don't worry, the concentrations are low.
August 15, 2013
It wasn't an objective of this well-focussed report, but it might have been helpful for lay readers to try to explain how a mutagen of this kind affects specifically the urinary system. Naively, one would expect a mutagen that reacts chemically with DNA to cause many types of cancer in many organs.
All I know is that this aspect of toxicokinetics is a difficult subject.
August 15, 2013
Not only it cause mutation,also lead kidney toxing.It is banned to use 10 years ago.Everything has merits,shortness,badthing----
August 18, 2013
I hope someone's thinking about doing a carcinogenicity assay on tiger bones, bear bile, and rhinocerous horn.
August 24, 2013
evidenceiskey: The purpose of my comment was to use evidence to show Ictor that his/her statement was inaccurate and it has little relevance to the article in question.
Your hostile attitude against Dionysius and me was uncalled for:
To start with, everything I said was simply stating the facts in an attempt to demonstrate that the article has little relevance to revealing the major cause(s) of cancer in China. It doesn't make me pro-alternative medicine.
Also, if you were afraid that I would deny evidence just so I can hold on to my narrow-minded believes, your worry is unnecessary. I am a molecular biologist, a geneticist and a supporter for the new atheist movement. I make a living by using evidence to support my findings. But I wish the so-called empirical evidence were as simple as you see it. Have you heard of “the theory-ladenness of evidence”?
Palaeontology (Cambridge Introduction to Philosophy and Biology) states that:
“The theory-ladenness of evidence can come in different strengths:
Your background theories might tell you where to look for evidence. For example, geological theories might tell you where to do your fieldwork if you want to study, say, the evolution of early land plants.
Your background theories might tell you why your evidence counts as evidence. For example, suppose you are looking at carbon isotope ratios in rocks in order to draw conclusions about the amount of photosynthetic activity in ancient oceans. You have to rely on background theories that explain how the carbon isotope ratios are related to photosynthetic activity.
Your background theories might tell you how to interpret what you see. Different scientists, with different theoretical commitments, might see the same thing but interpret it differently
Your background theories might influence or even determine what you see. Different scientists, with different theoretical commitments, might look at the same object but (somehow) see different things.”
You may think that natural science is “hard” and all evidence is black-and-white. However, “Natural science and philosophy are like two countries on a map with a common border that is well-marked in some places, disputed in others, and in still other places completely undefined.” In the past, there have already been way too many incidents where inaccurate reductionist approaches were adopted; correlation was mistaken for causal relationship; the method of induction was abused and ill-formed conclusions were made and executed based on the so-called “hard evidence” in the name of science. Do you know that racism was considered a legitimate science subject at Hitler’s time?
So please forgive me for not embracing the ideas in the aforementioned article in a hear beat. Because for me, science is really something special and I don’t want to see it turned into another religion.