From “bugs” to drugs

Wired’s running a story called “Turning Bugs into Drugs.” Unfortunately, the article’s opening two of sentences are almost completely wrong:
The dirty secret of pharmacology is that most medicines don’t work all that well. Stomach acids erode them, the liver filters them out, and the bloodstream shunts them away.
The real dirty secret here is that this is largely incorrect information. While it is true that some drugs’ efficacy is decreased as a result of metabolic processes, the actual truth is that pharmaceutical companies take these effects into consideration while designing drugs. Systemic drugs (those which enter the bloodstream and act on the body as a whole) are often inert in the molecular form that is introduced to the body via tablet, IV, etc. Then, when the body begins metabolizing the compound, the active form of the drug “falls out” so that it can go to work. In other words, it is the byproducts of the body’s metabolic processes that are actually the active forms of their respective drugs. So while the original form might “erode,” this could very well be part of the design.
Granted, not all drugs are like this, especially antibiotics, but many are. This error aside, the article has got some cool information about new drugs in the pipeline made from bacteria.
For cancer patients (these seem pretty out there):
Listeria monocytogenes causes deadly food poisoning, and the immune system responds in force at the first sign of the bacteria’s presence in the body. Stripping the bacteria of toxic genes and substituting ones that make molecules found in tumors may retrain the immune system to go after cancerous cells.
Status: Preliminary human trials later this year
Clostridium novyi is a relative of the bacteria that causes botulism. It doesn’t grow in live tissue at the edges of tumors but thrives deep in their dead interiors (where there’s no oxygen), eventually liquefying them. When the immune system cleans up the mess, it learns to kill living cancer cells.
Status: Animal studies
This cancer-fighter seems within the realm of possibility:
Salmonella typhimurium flourishes in tumors. By adding a gene that converts a relatively innocuous chemical called a prodrug into a toxin, it can be used to fight cancer. The prodrug goes to every cell in the body but only wipes out the ones inside the tumor.
Status: Preliminary human trials
A pet topic of mine since I have Crohn’s:
Lactococcus lactis is the bacteria used to ferment milk to make cheese. Tweak it to make IL-10 [Interleukin-10], and the bug passes through the stomach and makes medicine at the intestinal wall.
Status: Preliminary human trials
Modifying bacteria to make other products in the case of the Crohn’s and the last cancer treatment above has been done for years. E. coli is used to make insulin, for example, and has been made this way for a very long time. It is relatively easy to do because the bacterial genomes are much less complex than the human genome, and making modifications to it is relatively easy. I hope some of these treatments come to fruition.
New initiative for biomass fuel
Back in July, I reported on prisons in Rwanda using human waste as fuel. Now a new bill has been signed in Texas regarding how and where biomass fuel can be used. The bill also requires that more renewable energy resources be explored and developed over the next ten years.
In find it funny that the oil cartel (OPEC) keeps raising their prices for a barrel of oil, because by doing so, it makes alternative means of energy that much more attractive. Petroleum is a relatively price-inelastic item. Right now, raising oil prices does relatively little to curb demand, but I think a pricepoint will come where Americans will refuse to pay the exorbitant prices demanded of them. Then prices will come down again, but I the little environmentalist in me hopes that alternate fuel sources are more common before that happens.
But back to science. Researchers are trying to determine the most efficient way to convert waste into fuel.
One set of pens were paved with fly-ash, a byproduct of the coal-fired power generating industry, and the other manure was from unpaved pens. The manure was composted and test results from the two showed a large difference for several constituents measured, especially ash content, Sweeten said.
Ash, an unusable material as far as energy is concerned, was lower in the composted manure samples from the paved pens than the dirt pens – 20.2 percent compared to 58.7 percent. As a result, the low-ash manure had about twice the organic matter and heating value, he said.
Basically, they’re trying to maximize the energy yield by determining what, if any, type of paving should be used to cover livestock pens. Traditionally, the pens are paved with fly ash, but when the pens are scraped to collect the manure, the fly ash mixes with it, decreasing its burnability, and so the energy output per unit mass is lower. But experimental data shows that the opposite happens: there’s less ash in the paved pens than the dirt pens. I don’t understand why this is, perhaps because scraping a paved pen picks up less unburnable material than scraping dirt along with ash. Regardless, more experiments need to be conducted, including tests with composting and partially composting manure to determine how to get the most energy per unit mass.
In the United States, livestock waste is more prevalent than human waste by mass, and there are fewer inhibitions about using it as a source of energy than would be the case if human waste were processed. In many respects, Rwanda has a leg up on the United States as far as social stigmas are concerned.
The new Earth model
NASA has combined several models of the Earth to create a new picture of how our climate operates. The new system combines models of the atmosphere, ocean, land surface, and sea ice into one framework that promises to improve predictive capabilities for both short-term forecasts like one sees on TV to long-term climate models spanning a century or more.
Under a partnership, groups from NASA, the National Science Foundation (NSF), the National Oceanic and Atmospheric Administration (NOAA), the Department of Energy (DOE), the Department of Defense and research universities are using ESMF as the standard for coupling their weather and climate models to achieve a realistic representation of the Earth as a system of interacting parts, unifying much of the modeling community. ESMF makes it easier to share and compare alternative scientific approaches from multiple sources, uses remote sensing data more efficiently and eliminates the need for individual agencies to develop their own coupling software.
ESMF allows researchers to combine their efforts to create one comprehensive picture of the Earth. Whereas before, isolated groups worked on one part of the model, ESMF allows them to combine all of the pieces together, which would have been too large an undertaking for any one group to do.
The article goes into detail on how the pieces are layered together to create a cohesive whole.
Zinc fingers and gene therapy
There’s a new treatment for a few genetic diseases on the way. In a paper published in the June edition of Nature, Nobel laureate and president of CalTech, David Baltimore and Mathew Porteus of Sangamo BioSciences outlined a new approach to curing severe combined immunodeficiency disease (SCID, commonly known as “bubble-boy syndrome”) using zinc fingers to slice out defective portions of patients’ genes.
Specifically, the technique involves utilizing a built in cell DNA repair function called homologous recombination. Basically, cells have a built-in ability to repair DNA strands that have been cut using a sort of “master” DNA template. So if researchers snip out the defective part of the DNA, the strand is repaired using homologous recombination and a donor DNA template.
The technique is similar to a previous 2002 attempt to cure SCID, in which twelve patients were delivered a foreign gene using a retrovirus as the vector. Unfortunately, three of them developed leukemia and died, but the other nine were cured. The problem with that attempt was that sometimes the protein coded by the foreign gene not only vanquished the SCID gene, but also sometimes turned on a cancer-causing gene, because of the lack of specificity.
However the new approach doesn’t have this problem. The previous French attempt introduced the new gene randomly into the patient’s body. Zinc fingers, on the other hand, can only land at very highly-targetted spots on the patient’s DNA, and as such, they do not carry the risk of turning on cancer-causing genes.
“They’ve certainly raised the bar for gene-therapy safety,” said Scott Wolfe, a zinc-finger researcher at the University of Massachusetts Medical School in Worcester, Massachusetts. He points out that the early proof-of-principle work was highly toxic to the cells. The zinc fingers weren’t specific enough and they created so many double-stranded breaks in the DNA that a lot of the cells chose to commit suicide rather than try to repair all the breaks. “They really seem to have solved the toxicity problem altogether.”
The technique also shows promise for some types of cancer patients, AIDS patients, and even those with cystic fibrosis. Eventually if the approach is successful, zinc finger gene therapy could be used to target almost any genetic disease, with the only limitation being how much one could customize a zinc finger.
From waste to fuel
Leave it to third-world countries to invent new ways of recycling. In Rwanda, there is a prison near the Democratic Republic of the Congo that gets approximately one-half of their fuel for the prison by converting human feces into biofuel. Ironically, most of the prisoners at this prison are human rights violators (as are most of the prisoners in Rwanda as a whole). The overcrowded prison means that energy consumption is higher, and the amount of waste produced is greater as well.
Converting waste to biogas has improved three areas of the Rwandan prison situation. Firstly, it saves the Rwandan government nearly $1 million a year that it would have to spend on wood for fuel. Secondly, it has reduced the amount of waste being dumped into nearby Lake Kivu and other rivers. Thirdly, once the waste is processed, it serves as an odor-free fertilizer for the grounds.
The process of converting feces into usable methane gas starts out with a foul odor, but by the end, is odor-free. The program has been so successful that there are now biogas facilities in nearly half of the thirty prisons in Rwanda, and they produce nearly half the necessary electricity to power the prisons.
The facilities resemble giant beehives, and is used widely throughout the world. The process is self-sustaining:
The process requires putting a given amount of human or other animal waste into a “digester,” which ferments it using bacteria to release methane gas that can be captured and then burned as fuel. Attached is a “compensating chamber” that replenishes the supply of bacteria to keep the operation self-sustaining.
In four weeks, 100 cubic meters of waste can be converted into 50 cubic meters of fuel, which is used to make electricity and is even used as cooking fuel. The prisoners apparently aren’t deterred by using their own waste to cook with: they see that it works, and so they want to use it.
Rwanda isn’t the only country using waste as fuel: some Nepalese have begun to use it in their homes, and the Swedes use it to power trains. Rwanda is, however, probably the most unique country to use biogas. There’s something poetic about human rights violators using their own waste as a means to create electricity and cook. Now if only such a system would be put into place in the United States. Alas, most first-world countries have other, too well-established means of producing power, and their citizenry would have a collective heart attack if human waste was used as a means of cooking food for human consumption. Third world countries, on the other hand, have no such inhibitions, and it should come as no surprise, then, that they would come up with a way to solve waste problems in an innovative, environmentally friendly, and cost-effective manner.
If you’re curious, you can find instructions on how to build your own biogas plant here.