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Biotech Makes the News
hoppy wrote to us in regards to the recent EE Times article about a tuberculosis detecting biochip. The United States and Russia are teaming up to make the chip, as variant drug-resistant strains are infecting thousands in Russian jails, and making a big comeback in poorer areas in the US. The chip will be used to identify the strain of TB, so that appropriate treatment can be used, rather then the shotgun approach In other news, James Clark, co-founder of SGI and Netscape has given 150 million US to his former school, Stanford. The donation is to be used just for biotech.
There were actually two chips announced this last week. The drug diagnosis chip from Argonneand a research-based expression chip from Peter Small's lab at Stanford.
The Argonne chip is a competitor to Affymetrix/BioMerioux's TB chip which is also still in development. What these gizmos are designed to do is DNA sequencing by hybridization. The TB genome is sequenced and we roughly understand how many of the antituberculosis drugs work and what genes mutate to confer drug resistance (mostly). The traditional (and only FDA approved) way is to grow the patient's TB specimen in the presence in each of these drugs and see if growth is inhibited. For strains that are multi-drug resistant (MDR), that can take many weeks or even months to correctly diagnose. In the early days of the MDR outbreak in NY city in the early 90's, many of the patients were dead before the results were available (aggrevated by HIV/AIDS in the pre-protease inhibitor days).
Peter Small's chips are designed to understand which genes are turned on/off under different conditions. Their paper in the Oct 26th issue of PNAS is their results using these chips on TB treated with isoniazid (the first anti-TB drug).
So molecular diagnostics is a goal of everyone's. Here in our lab we use both the traditional methods and then direct DNA sequencing as an experimental program. Direct DNA sequencing is a bit tedious and can get expensive for each hunk of the TB chromosome you need to sequence to cover all the potential sites for drug-resistance conferring mutations. Arrays let you "do it in one shot".
And Argonne's reported ability to reuse these things 50x would be a huge thing. George Soros is probably footing some of this bill since he's been donating a ton of cash to try to check the expansions of TB in post-cold war Russia. Their prison system is a real nightmare and their "tough on crime attitude (much like the US!) doesn't mind if these prisoners give each other TB and they end up dying. But at least a few of these prisoners do get released and then the problem goes into the general population. The TB we're seeing from Russian immigrants now is really strange. It's not always resistant to the first line of drugs used (safer and more effective) but resistant to many of the second line drugs (full of nasty side effects, less effective, and much more expensive). Wealth individuals in Russia seem to be assuming they have drug resistant TB and just starting in the on the second line drugs.
Our prison system was caught a bit off guard when TB resurfaced in the 80's. They've *vastly* improved now and while TB is still diagnosed in prisons, the transmissions seem to be checked. Here in NY about 20% of our prison population is HIV+ so keeping TB checked is really important.
Problems with these chips arise when you have mixed populations of TB in a patient. Some cells have the mutation that causes resitance, and some don't. Since all these arrays start off with a PCR amplification reation, if the susceptable cell's DNA gets amplified over the mutant ones, you might get the wrong diagnosis. Or if a patient has two different strains of TB in them (can happen but mostly in immunocompromised individuals). But this is much less a concern than in the situation of HIV where these molecular diagnostics sometimes run into trouble.
With 1 billion people in the world infected with TB (and here in NY, it's nearly 1 out of 15...though most will never come down with "active" disease even untreated), don't assume it's a Russia/third world/poor thing!
Cheers!
Now if Biotech was really that employable you would have gone into biotech instead of working at Andover and we all know you're a biotech freak. Don't get these kids fired up about something which is almost entirely post-docs who can't find jobs. After the first 6 years of grad school you realize how increadibly tightly pigeonholed it is. Then after selecting one small, discreet area of biotech and pigeonholing yourself you realize that despite all the hype, the one discrete area of the one gene that got your postdoc buddy that day job in North Dakota was one base pair away from yours so you didn't get it. None of the grad students I've encountered are happy and they all wish they were in CS. Now MD degrees, if you're famous enough to get one, have an easier time. The resources available to MDs makes postdoc work look like tinker toys.
However, the reason we're in such shit from M.Tuberculosis and S.Aureus is the ridiculous overuse of antibiotics. Vancomycin -- the antibiotic that kills anything -- is proving less than effective against some strains of both. This is a problem that's entirely of our own making, and one that's being exacerbated by the overuse of animal feed, the growing of GM crops and people pestering their doctors for antibiotics and then not taking the full course.
It`s got nothing to do with GM crops. But it`s certainly to do with antibiotics in animal feed. Farmers routinely stuff their animals with antibiotics even when they`re not ill, because it makes them grow faster. If you can be bothered ploughing your way through this, there`s a lot of good stuff there. The most important thing I want to bring out of it is that many strains of antibiotic-resistant bacteria currently populating hospitals have been traced (by techniques related to DNA fingerprinting) to farm animal bacteria.
Certainly in the UK, the problem of antibiotic resistance is severe. I never want to fall seriously ill here. The Glasgow Royal Infirmiary, just a few yards away from where I work, has the worst record in the country for antibiotic resistance, and you have a fairly high chance of going out of there with something far worse than you went in with. The hospital environment is overrun with `superbugs` (bacteria resistant to all hospital antibiotics), and iatrogenic diseases (iatrogenic=caused by doctors) are becoming more common because of this.
The solution is, of course, to design new antibiotics. But these may in turn fail in the same way, even if they`re not given to the animals. Since 1950, animal antibiotics have been kept separate from human antibiotics (as in, they`re different chemicals), and yet they`re still sufficiently similar to enable the resistance mechanism to work against both. It`s a biological arms race. Our survival depends on developing new antibiotics. The bugs` survival depends on overcoming them. The trouble is that a resistance mechanism may (depending on the mechanism and the drug) confer resistance to a whole swathe of antibiotics in one go. And it spreads fast. Most of these resistance genes are on plasmids, which can be transferred from bacterium to bacterium as well as down the generations (which are fast as it is: a bacterial population will, under optimum conditions, double every 20 minutes).
Overprescription of antibiotics is, of course, also a factor, and for this I tend to blame the patients rather than the doctors. But the reason that antibiotic resistance is so rife in hopitals is not overpresciption, at least not here (it tends to be patients coming to their GP with a cold and complaining if they don`t get a prescription for something - perhaps vitamin pills ought to be available on prescription..). It`s because there are so many ill people (who probably do need antibiotics) that there is a considerable selection pressure in favour of antibiotic-resistant bacteria. Once it gets in, it`ll spread like wildfire, and become stronger.
I don`t think there`s such a thing as an antibiotic that no bacterium can become resistant to. If nothing else, the bug can change its cell membrane to prevent the antibiotic from getting in. But if we find new types on antibiotic, that work in a way that no current antibiotic does, then it`ll take a lot longer for the bugs to become resistant. And that gives us more breathing space.
Two comments, actually.
1) PacketBioStorm. Every time I see an announcement about Biotech, I feel like I'm seeing a convergence between the both utterly dissimilar and disturbingly reminiscent fields of Network Security and Human Biology. Beyond the obvious "virus" appelation, much of the technology being applied to deal with both script kiddies and randomly evolved pathogens (you decide who you'll respect more) has to do with quick identification of massive streams of information through ingeneous code. Biotech adds another layer, since organic materials must be parsed, but it's still the same old schtick.
Sorry to the speakers at Linuxworld, incidentally, but the Human Genome Project is easily the world's largest reverse engineering effort. And will you take a look...a battle between open and closed source. Who's surprised?
2) So Jim Clark has specified the task his money is to be used for. There's actually alot of controversy about that--should donors be able to demand budget parameters? To what degree? Should donations be revokable if, say, a professor at the university violates some specific usage clause? Keeping in mind that most of our college educations either are, were, or will be endowed quite heavily by Alumni and Corporate Sponsorship.
Also remember that Gates intends to donate his fortune in entirety, and that Microsoft is a tremendous benefactor of educational institutions across the country. Think about what Clark's specification means in that context.
There are no easy answers, are there?
Yours Truly,
Dan Kaminsky
DoxPara Research
http://www.doxpara.com
Anything that'll combat TB is a good thing, and this biochip could well be a vital part of the anti-TB arsenal.
However, the reason we're in such shit from M.Tuberculosis and S.Aureus is the ridiculous overuse of antibiotics. Vancomycin -- the antibiotic that kills anything -- is proving less than effective against some strains of both. This is a problem that's entirely of our own making, and one that's being exacerbated by the overuse of animal feed, the growing of GM crops and people pestering their doctors for antibiotics and then not taking the full course.
I realise that this could be seen as somewhat offtopic, so I apologise if it pisses you off. But it needed to be said. Again.