Another from C&EN

my current understanding of microfluidics

Microfluidic devices are systems for manipulating fluids in very small scale channels and wells. Scientists struggle to study cells and tissues outside the body, because the Petri dish environment is unlike the natural environment in which they exist, microfluidics have enabled scientists to mimic specific properties of biological systems and show us completely new ideas. The microfluidic devices depend on existing technology from the making of computer chips and similar products. Microfluidics can function in a way similar to the small capillaries of the circulatory system and lungs, and are useful in other ways because “a lot of our body is microfluidic, little tubes and ducts and blood vessels.” The devices will enable studies from the body in a controlled test tube, laboratory environment; in vitro. The controlled part of the environment is derived from the type of flows possible in the microfluidic devices. Laminar flow, where fluids flow side by side without mixing, is more prominent than convective flow, which is temperature driven and mostly affects the Petri dish type set up.
There are a few systems for which this technology shows exceptional promise; they include stem cells, neural system, vascular system, and cancerous tissues. One example of research done was studying blood clotting. The scientist Ismagilov used the microfluidic systems to show that clotting occurs based not only on the size of the patch of clot activating factors, but also its shape. For many of the studies the ability to recreate these small systems, allows for proper testing and screening of drugs. Having fluid mechanics similar to that of the lung allows for greater research on diseases like cystic fibrosis, asthma and pneumonia. In tissue engineering the scientists can study how cells communicate during the formation of breast cancer tumors. In flowing systems, and in conventional culture systems, they cannot look at signals in such detail. The technology is not perfect completely, as engineers worry that the biologists will not be able to use this as a tool in labs without great accommodations, like how we can use pipettes relatively easily.
The use of semiconductor technology is wonderful, in part because it has existed for decades, and so is as inexpensive as one could hope. That this technology “makes intuitive sense” is notable to me because intuitive reasoning is part of what we discussed in class as a characteristic of a good scientist. Also because we are using existing ideas, it is more likely that scientists adapt on it and expand the concept even further. Often when asked if they are interested in lab research, people will say that the lab research isn’t interesting or is less scientific because it was performed on test subjects not identical to the final patient. In developing these ideas scientists often devote resources to things which are at first not the obvious answer. Because our neurons are not identical to rat neurons there is sometimes dissatisfaction in the mass population when we use them in tests. There is also so much power in the ability to control flow through vessels and ducts, because this includes both hormones and enzymes. Using microfluidics allows for more efficient testing of the effects and causes of many diseases.

(also in response to reading C&EN)

In response to an article in C&EN magazine about Tuberculosis.

Tuberculosis is a global health emergency, and the areas hardest hit are in the developing world. This poverty and inadequacy of healthcare exacerbating factors, these along with HIV/AIDS increasing contraction and mortality of TB have made it the second leading infectious cause of death. Most people who don’t have HIV are not infected when exposed to TB, but the already weakened immune system makes it more prevalent in those individuals who do have HIV. Of those infected, ninety percent develop a noncontagious dormant form of TB, worldwide there are two billion people who have this, it can reactivate decades later under certain circumstances such as a suppressed immune system. This prevalence is a big problem if the drugs used to treat the disease stop being as effective. Research and Development of TB had declined after the initiation of effective treatments, but by the nineteen eighties there was cause for great concern. The HIV crisis played a part in encouraging the current TB emergency. There are many obstacles in treating TB, “WHO recommends a treatment regimen for active, drug-susceptible TB consisting of four antibiotics-isoniazid, refampicin, ethambutol, and pyrazinamide-taken for two months, followed by isoniazid and rifampicin for another four.” This regimen helps rid the body of so-called hidden bacteria, meaning it helps prevent that one straggler from coming back decades later. Inherently problematic is when this initial treatment fails because the bacteria have become resistant to any of the drugs, this first level of resistance is called multi-drug-resistant MDR TB. Increasingly common in China, India and the former Soviet Union, it can be combated, “albeit sometimes less than 60% of the time-by taking one of more of a group of second-line drugs, some with serious side effects for up to two years. The third type of TB is XDR, extensively drug resistant. Another obstacle is trying to treat people who were more susceptible to TB because of HIV, which has its own drug regimen and so the scientists must combat drug-drug reactions.

There are many people working to combat this problem, alliances between pharmaceutical companies, scientists, academics, government and industry officials Philanthropists all operating to try to help the people this is affecting. Their goals are to get “better diagnostics, more effective vaccines, and oral drugs with limited side effects that can shorten treatment, combat resistant strains, work with HIV drugs, and treat latent infection.” These will, by making the regimen more consistent efficient and easier to follow, hopefully cause a decrease in infection, the development of resistant strains and fatalities because of those. Whether the current ambitions are attainable or not, the community is gaining something that will be a great tool, knowledge, they are learning specifically about how vaccines are made, what factors are involved and the great efforts that can be made to the benefit of people. Science is dependent on people working together, which is why it is so tragic that R&D had been “neglected not only by pharmaceutical companies, but also by granting agencies…the stock of basic knowledge we can build on to select our targets and understand the biology of the disease is very much less than in other areas, such as cancer, where we can count on the work of thousands. So we must work with partners in academia to catch up.” The scientists have been studying millions of compounds, and are developing several possible drugs which are being researched heavily. They are comparing the effectiveness and recoil of each of them, and determining which could be studied further and how. They developed drugs that will replace parts of the existing regimen and make it more efficient. Statistical analysis plays a huge role in whether drugs are fit or not, and part of the issue is that the current therapies success rate is 95% and in order to determine if there is a significant change, huge trials are necessary, with restrictions and complications to an extreme.

The drugs are developed looking at what they target, and how they’d react with antiretroviral drugs. All of these new drugs are developed through an increasingly intimate understanding of how TB works. These are true scientists, and the test of their success will ultimately be life and death. Before a treatment can be deemed effective, it must be convincing enough to get all the effected populations, industries and governments to change their programs. The never ending issue of money comes back into play when you get past the funding needed for research and consider what it costs to get these new therapies to those affected.

Even after funding and resource sharing between those mentioned in the above alliance, the drug must still be manufactured, marketed and distributed, the limited incentives (due to necessity of low priced goods) makes it a burden to sell or make. To take part in this more selfless than most of the pharmaceutical practices we discuss, and may help to even out the field in that regard. I did not know about latent TB or the scale by which the world is effected. I never would have imagined that two billion people have the latent TB, or that it could come back and activate decades later. I also didn’t know the extent of treatment required in any of the situations. The effort going into fixing this problem is remarkable. The specifics of the drugs being researched is really neat too, because they target different parts of the TB, and so have different effects. They are looking at destroying proteins and interfering with mycolic acid production, stopping the ATP synthesis of only the unwanted bacteria, and growth inhibitors in cell wall synthesis. The need to communicate is highly evident in this article, it shows how not having information available to researchers sets things back severely. This brings to mind what we learned about the value of journals, for disseminating information and ideas and enabling people to innovate without having to repeat the same mistakes. The way they are researching is very conscientious also, with people based in the environment and culture affected the disease, as well as considering healthcare circumstances, the conditions under which the treatment is administered. This growing theme of being connected, and looking at things from a wide perspective is part of what makes this endeavor just a bit more possible. “No single entity has enough resources on its own, and we realize it is going to take the best efforts on all our parts to be successful.” Gail H. Cassell. Aligned with the unity in life abroad, science also depends on teamwork, innovation and communication.