An interview was recently published in Lab Times with Peter Lawrence, who discusses what is wrong with science research - a subject that I've been talking about a fair bit at work, where the majority of other writers have done the PhD/postdoc thing then had nowhere else to go. Its quite an amusing article if you've been in the science game, with observations such as that papers in Nature, the most esteemed journal which everyone wants to get into, are so dense as to be actually unreadable. And that scientists have become little more than paper-spewing machines, where the publication becomes the end in itself rather than any idea of a pursuit of knowledge.
The basic challenge is this - get at least one first author paper out in the 2 (3 if you're lucky) years of your postdoc or thats it, you're out of science. And if you do get it, you get another 2 years (well, more like 18 months if you're going to start work on the next grant). And so on. The ultimate aim is to get your own lab group to manage, at which point you will never see the lab again and instead become buried under paperwork, meetings and bureacracy.
No wonder I, and the majority of people I did my PhD and postdoc with, have come out of science.
The other side of the problem as far as I can see it, is that there are far too many people now in science, in particular biology (especially molecular biology - my ex-field). More PhD's than there are interesting things to study, or at least when they have graduated.
Of course, I was a bit foolish in concentrating almost solely on my studies, and later my research, without really thinking where I was going, what the job scene was likely to be, and whether I was picking up enough competitive skills. Fortunately I wrote a couple of reviews during my postdoc, which must have at least helped my current job as a medical writer; my ability to do PCR and subcloning blindfolded and plate out thousands of yeast transformations couldn't even get me a maternity-leave technician job in a hospital genetics department, never mind another research post.
I don't blame anyone though, I was too focused on small things without seeing a bigger picture. Actually, I would criticise the sciences for that - I might have had much more interesting ideas for my PhD if I'd had more contact with the physics/technology/mathematics department for instance and we'd come up with a design for an artifical pancreas. It would be nice to have a bit more confidence to go an make contacts like that, but unfortunately most researchers are so absorbed into their own fields that such cross-discipline collaboration (or even awareness, at all, at what is going on - the splintering of science into ever-more ridiculously obscure fields - compare to the polymaths of old who knew a bit about everything).
Showing posts with label Research. Show all posts
Showing posts with label Research. Show all posts
Monday, 9 May 2011
Tuesday, 22 September 2009
Curing cancer with bacteria
It was my turn to do journal club today, which is where we do a talk to our lab group about a science paper that has recently come out. Today's title was "Sequential treatment of drug-resistant tumors with targeted minicells containing siRNA or a cytotoxic drug", by MacDiarmid et al., and it was a strange, though interesting one. (Reference: Nature Biotech 27 643 - 651 (July 2009))
I've had a long standing interest in gene therapy, which is where you would use genetic factors to cure a condition, rather that just administering a drug. This paper focused on an alternative treatment for cancer. A lot of tumours become resistant to the drugs used for chemotherapy, which is often due to a mutation which leads to the cell making lots of a certain type of protein that prevents the drug taking action. Increasing the dosage may only make the patient sick due to side-effects of the drug, while the tumour survives.
MacDiarmid et al. used a combination of small interfering RNA, or siRNA, to reduce the resistance of a tumour cell to drugs, and a novel method of delivering the siRNA directly to the tumour, namely bacterially derived minicells. Minicells are basically bacterial cells lacking any insides that can be loaded up with genetic material or chemical compounds. They are formed from a mutant strain of bacteria that does not divide properly. Usually bacteria have a main chromosome, but minicells lack this and are very small as a result. They are really not much more than a sack surrounded by a lipid (fat) membrane. This can be loaded up with a drug for instance by incubating the minicells and the drug together. The minicell can be programmed to deliver its contents to a target cell by the use of a special antibody. The antibody recognises part of the minicell wall, and also an antigen presented by the target cell, which in this case is the EGF-receptor (EGF = epidermal growth factor) which is found in high concentrations on the outside of many types of cancer cell.
In this case, the target cell was a human tumour that had been grafted onto some unfortunate mice, and was expressing the drug resitance gene MDR1 (for multi-drug resistance). The Minicells get into the tumour cells and get eaten up by the cell, but release the siRNA payload. This activates the RNA silencing system to prevent expression of the MDR1 gene, and thus make the tumour drug-susceptible again. They then followed this up with another treatment, where the minicells were loaded with a drug which could then kill the tumour off.
As for the results, they treated mice bearing various types of tumour with the minicells carrying anti-MDR1 siRNA and then used minicells carrying a drug. The tumours regressed in size, and the mice survived, while the treated ones did not. The controls used were good - minicells which were not targeted to the tumour, ones which has a nonsense siRNA, which has basically a random sequence so does not affect any gene, and various combinations of minicells and standard drug administration. None of the control treatments had any effect.
So this strategy has a lot of potential in humans, assuming that people could accept a treatment involving what is basically the outside of a bacterial cell, and some genetic tinkering. I would imagine there would be a lot of problems with the human immune response as well. One thing the authors did not show was whether the treatment would work against a tumour of mouse origin, as they only used grafted human tumour cell-lines. Their strategy was to use an anitbody against EGF-r, which although it is expressed highly in tumours, is also expressed elsewhere in the cell. They used an antibody against the human EGF-r to target the minicells, which probably doesn't react very well with EGF-r of mouse origin; a good control would have been to use an antibody against mouse EGF-r. Also, although the treated mice survived, it wasn't clear whether the tumour had regressed or been killed off. I suppose if it extends your life by a few years, it still would make a good treatment, but there are obviously a lot more studies to be done.
I've had a long standing interest in gene therapy, which is where you would use genetic factors to cure a condition, rather that just administering a drug. This paper focused on an alternative treatment for cancer. A lot of tumours become resistant to the drugs used for chemotherapy, which is often due to a mutation which leads to the cell making lots of a certain type of protein that prevents the drug taking action. Increasing the dosage may only make the patient sick due to side-effects of the drug, while the tumour survives.
MacDiarmid et al. used a combination of small interfering RNA, or siRNA, to reduce the resistance of a tumour cell to drugs, and a novel method of delivering the siRNA directly to the tumour, namely bacterially derived minicells. Minicells are basically bacterial cells lacking any insides that can be loaded up with genetic material or chemical compounds. They are formed from a mutant strain of bacteria that does not divide properly. Usually bacteria have a main chromosome, but minicells lack this and are very small as a result. They are really not much more than a sack surrounded by a lipid (fat) membrane. This can be loaded up with a drug for instance by incubating the minicells and the drug together. The minicell can be programmed to deliver its contents to a target cell by the use of a special antibody. The antibody recognises part of the minicell wall, and also an antigen presented by the target cell, which in this case is the EGF-receptor (EGF = epidermal growth factor) which is found in high concentrations on the outside of many types of cancer cell.
In this case, the target cell was a human tumour that had been grafted onto some unfortunate mice, and was expressing the drug resitance gene MDR1 (for multi-drug resistance). The Minicells get into the tumour cells and get eaten up by the cell, but release the siRNA payload. This activates the RNA silencing system to prevent expression of the MDR1 gene, and thus make the tumour drug-susceptible again. They then followed this up with another treatment, where the minicells were loaded with a drug which could then kill the tumour off.
As for the results, they treated mice bearing various types of tumour with the minicells carrying anti-MDR1 siRNA and then used minicells carrying a drug. The tumours regressed in size, and the mice survived, while the treated ones did not. The controls used were good - minicells which were not targeted to the tumour, ones which has a nonsense siRNA, which has basically a random sequence so does not affect any gene, and various combinations of minicells and standard drug administration. None of the control treatments had any effect.
So this strategy has a lot of potential in humans, assuming that people could accept a treatment involving what is basically the outside of a bacterial cell, and some genetic tinkering. I would imagine there would be a lot of problems with the human immune response as well. One thing the authors did not show was whether the treatment would work against a tumour of mouse origin, as they only used grafted human tumour cell-lines. Their strategy was to use an anitbody against EGF-r, which although it is expressed highly in tumours, is also expressed elsewhere in the cell. They used an antibody against the human EGF-r to target the minicells, which probably doesn't react very well with EGF-r of mouse origin; a good control would have been to use an antibody against mouse EGF-r. Also, although the treated mice survived, it wasn't clear whether the tumour had regressed or been killed off. I suppose if it extends your life by a few years, it still would make a good treatment, but there are obviously a lot more studies to be done.
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