Drugs in the water: Behold the power of synergy

Byoliveridley

funky MathES&T Online News: Can drugs found in water harm humans?

Researchers agree that aquatic species face the greatest risk from exposure to low levels of pharmaceuticals, such as synthetic hormones, which can act as endocrine disrupters at environmental levels. However, little is known about the potential human health effects arising from complex drug mixtures.

Well, it is often more difficult to analyze complex mixtures because Experimental Design 101 makes you want to isolate the effects. And when you do compounds one by one in series, the tendency is to always add them up from the individual experiments. Unfortunately, body chemistry is not like that. I’ve always wanted to design a study that started complex and then tried to isolate later.

To his surprise, Pomati observed that this mixture of drugs at environmental levels inhibited the growth of human embryonic kidney cells. After 48 hours of exposure, cell proliferation was reduced by 10–30% compared with controls. However, no inhibition was observed when cells were exposed to only the toxic cancer drug at environmental levels.

Well, that seems conclusive enough, but here comes the “Experimental Design 101” Scold:

The results show that the growth inhibition is not due to the single most cytotoxic compound alone. But that does not conclusively prove that synergistic or additive effects exist between drugs in the mixture, cautions Thomas Heberer of the Institute of Food Chemistry at the Technical University of Berlin. To show that the individual drugs behave additively, Heberer suggests that researchers should analyze the effects of compounds with a common mode of action, such as antibiotics, alone and in various mixtures.

No, No, and No. Doing this presupposes that you know that mechanism of action, meaning you’ve half answered your question. The question Heberer is trying to answer is “do individual drugs with the same mode of action behave additively”. The question Pomati is trying to answer is “Can we demonstrate cytotoxic effects of a cocktail of drugs at ambient levels in a laboratory setting”? These are two completely different questions and Pomati’s question is more valuable at this point in time. Heberer’s strategy, on the other hand, will keep a lab well funded for years to come! But, it is very much the final step.

It is more important at this point in time to demonstrate other effects such as endocrine disruption, mutagenicity, etc in the lab at environmentally relevant levels of mixtures. Then we can get a better handle on which  effects are relevant and which ones to ignore.

Similar Posts

  • | |

    Indian Parliament Discusses Climate Change

    Byoliveridley

    India stresses on Kyoto standards-India-The Times of India

    The discussion on global warming in Parliament will end with the statement of environment minister A Raja, possibly on Monday. He is bound to restate the country’s position on climate change in the international arena — that countries must bear “a common but differentiated responsibility” for climate change, a phrase that is the central pin of the Kyoto Protocol.

    De-jargonised, it means, while every country is adding to the problem, there are some that are more responsible than others, and should, therefore, bear the burden and costs of cleaning up more than the smaller culprits

    More highlights…

    The US, between 1950-2003, emitted 10 times more carbon dioxide than India did. Europe emitted 8.5 times more. Yet US and Australia, two of the biggest emitters of greenhouse gases, have refused to ratify the Kyoto Protocol (which asks developed countries to reduce their emissions) on the pretext that developing countries like India and China are not undertaking emission cuts.

    Worse still, if one looks at per capita emissions from different countries, which is a more equitable way of calculating emissions if one was to go by the principle that each person has as much right to the atmosphere as another, then India ranks a mere 120 compared to US which ranks 6 and Australia 10 on the culprits’ list. This is taking the emission levels of 2003.

    Well, they are right, and they are wrong too. The developed world has a lot to more to cut back on and should make the bulk of the cuts. But India and China also need to grow using current state of the art knowledge, not using the 1950s coal intensive, energy inefficient model of increasing supply without paying attention to demand. We have also come to realize that IPCC reports, due to their consensual nature, are conservative. So, they will tend to understate the effects of climate change and overstate the costs. It may not be as expensive in India and China as long as attention is being paid to hw the infrastructure is being developed.

  • Canada's only proposed Carbon Targets in Danger

    Byoliveridley

    Bill C-311, Canada’s Climate Change Accountability Act, is back in the “news” (no silly, not the media, who have more important things to worry about). I had written about this before the Copenhagen meeting. This bill sets Canada up with greenhouse gas emission reduction targets that would put Canada in a respectable mainstream position, 25% below 1990 levels by 2020, 80% below 1990 levels by 2050. But the Conservatives, in one of their classic legislative gambits, have forwarded the vote for April 14th, Wednesday. If the bill doesn’t pass here, it’s dead, and 4 years of countless committee readings, and multiple votes to pass would be wasted. And Canada will not have any climate change legislation whatsoever.

    Serious business, isn’t it? Climate Action has more, including what you need to do (I know, short notice, that’s apparently how important decisions get made around here).

    The Liberals hold the key. It was they who voted with the Conservatives the last time to scuttle the pre-Copenhagen vote. As of writing this post, no official word from the Liberals on their position.

    A call to Michael Ignatieff’s office, (613) 995-9364 gives me little hope of passage. I was told that the MPs had met, that Mr. Ignatieff would not be voting (apparently, because it’s a private member’s bill, leaders don’t vote, weird). Also, the official position of the party is that because it is a private member’s bill, that every MP would be free to vote on their “conscience”. Given that the Liberal party could not even defend women’s health in a recent whipped vote, I wonder where their conscience is on this.

    A call to David McGuinty’s (the Liberal Environmental Critic) Office, (613) 992-3269, elicited the rather helpful response that they would not be commenting on their stand till after the vote.

    Of our local MPs, both Denise Savoie (NDP) and Dr. Keith Martin (Liberal) will be voting to preserve the bill, they are on record saying this at a forum on climate change last week. Of course, Gary Lunn (Conservative) is not part of the equation here, pointless.

    So, call, call and call away, the Liberals need to hear about this. They don’t appear to understand the most basic rule of opposition politics, you get no points for supporting the government, except from pundits in the mainstream media. Only if you inflict some defeats on the government will the people of Canada take you seriously.

    David McGuinty – (613) 992-3269
    Michael Ignatieff – (613) 995-9364

    As always, remember that it is the Liberals that will be blamed for this bill’s demise, we all know the Conservative position on climate change. The NDP and Bloc Quebecois have voted repeatedly to pass this legislation. It is Michael Ignatieff’s Liberals who will stand in the way of Canada’s environmental progress.

  • Oceans of Carbon Dioxide?

    Byoliveridley

    Well, possibly the biggest climate change science news of the day, sequestration with a twist. Now if we can only get those friendly little carbon dioxide molecules to march down a couple of miles down to the ocean sediments to sequester themselves! But seriously, it will take a lot of pumping.

    Permanent carbon dioxide storage in deep-sea sediments — House et al., 10.1073/pnas.0605318103 — Proceedings of the National Academy of Sciences

    Stabilizing the concentration of atmospheric CO2 may require storing enormous quantities of captured anthropogenic CO2 in near-permanent geologic reservoirs. Because of the subsurface temperature profile of terrestrial storage sites, CO2 stored in these reservoirs is buoyant. As a result, a portion of the injected CO2 can escape if the reservoir is not appropriately sealed. We show that injecting CO2 into deep-sea sediments <3,000-m water depth and a few hundred meters of sediment provides permanent geologic storage even with large geomechanical perturbations. At the high pressures and low temperatures common in deep-sea sediments, CO2 resides in its liquid phase and can be denser than the overlying pore fluid, causing the injected CO2 to be gravitationally stable. Additionally, CO2 hydrate formation will impede the flow of CO2(l) and serve as a second cap on the system. The evolution of the CO2 plume is described qualitatively from the injection to the formation of CO2 hydrates and finally to the dilution of the CO2(aq) solution by diffusion. If calcareous sediments are chosen, then the dissolution of carbonate host rock by the CO2(aq) solution will slightly increase porosity, which may cause large increases in permeability. Karst formation, however, is unlikely because total dissolution is limited to only a few percent of the rock volume. The total CO2 storage capacity within the 200-mile economic zone of the U.S. coastline is enormous, capable of storing thousands of years of current U.S. CO2 emissions.

  • Climate change infographic

    Byoliveridley

    This infographic came my way via Learnstuff and it looked interesting. I have a love-hate relationship with infographics and this one evokes the same feelings of “I really appreciate the effort someone put into this and it looks great” vs. “how is this going to influence our policy makers, or create the intensity (read this link, it’s really good stuff by David Roberts of Grist) that is required to foster the system change we need”?

    Climate-Change

  • |

    Jeffrey Sachs on climate change induced water shortages

    Byoliveridley

    Depressing reading for a Sunday morning. He does not offer too many solutions, but it will take a lot of local work to mitigate these disasters. Of course, I can’t see the US or Europe offering asylum to climate change refugees!

    Climate Change Refugees: Scientific American

    Human-induced climate and hydrological change is likely to make many parts of the world uninhabitable, or at least uneconomic. Over the course of a few decades, if not sooner, hundreds of millions of people may be compelled to relocate because of environmental pressures.

    To a significant extent, water will be the most important determinant of these population movements. Dramatic alterations in the relation between water and society will be widespread, as emphasized in the new report from Working Group II of the Intergovernmental Panel on Climate Change. These shifts may include rising sea levels, stronger tropical cyclones, the loss of soil moisture under higher temperatures, more intense precipitation and flooding, more frequent droughts, the melting of glaciers and the changing seasonality of snowmelt.

    Technorati Tags: ,

  • |

    Health Canada report ties asbestos to lung cancer

    Byoliveridley

    Health Canada sat for more than a year on a report by a panel of international experts that concludes there is a “strong relationship” between lung cancer and chrysotile asbestos mined in Canada.

    Health Canada received the report in March 2008, resisting calls from the panel chairman to release the findings despite his plea last fall that the delay was “an annoying piece of needless government secrecy.”

    Canwest News Service obtained the report under Access to Information legislation, but the request took more than 10 months to process.

    Vancouver Sun

    Yes, dog bites man anywhere else except Canada, which has a hard time accepting that it routinely exports products that kill people. The “annoying piece of needless government secrecy” is neither needless or annoying. It protects a dying industry with a few, powerful stakeholders in Quebec, an important swing political province, so there’s need for it! Annoying – your seat “buddy” on the bus yammering on their cellphone, cancer, well, I don’t know, you tell me!

    Expect little to change from this report. It does mention that there is little danger from “Canadian exposure levels”, conveniently forgetting that 90% of the export is to developing countries where there are fewer safeguards. This feeds into the Canadian government line that “chrysotile” is safe if used correctly. If you think this line of reasoning is familiar, it is. The tobacco industry used it routinely till recently.

    Shame.
    n