For the Sake of Science

One of the hallmarks of quacks is that they’re willing to latch on to any bit of science that shows even the most remote, most distant promise. One familiar quack did this for a preliminary study not too long ago. And other quacks do it all the time. They hear about some result which indicates some positive benefit from something – usually a berry or herb – and they go nuts. Forget that they reject just about everything else science has to tell us. If it fits into their paradigm, it must be true.

But of course they’re jumping the gun. Again and again a study will come out which shows promise for some substance that will help in the fight against this or that disease, but once a few more groups start taking a look, things fizzle out. Often studies will even get to the clinical stage, only to turn out to be failures. (“Failures” in the sense of not working, not in terms of science.) Companies usually are decent at protecting themselves from getting that deep if there is no benefit to be had, but they aren’t perfect.

I go on about this because I am currently reading a review article about the protein p53. It is a protein which is involved in tumor suppression. When it mutates, usually by missense mutation, it becomes involved in tumor growth by virtue of loss of function, though evidence strongly suggests that it also confers a gain of function in terms of cancer growth. I’ve written about other tumor suppressing proteins here.

I had to stop when I got to a section about post-translational modifications of the protein:

Post-translational modifications of p53 such as phosphorylation, acetylation or sumoylation have been shown to be essential in determining and regulating p53 activity in vitro. However, their effects in vivo remain difficult to assess. Sabapathy (S1) generated a ‘knock-in’ mouse strain replacing the serine 312 residue, equivalent to the human serine 315, by alanine (S312A) to abolish phosphorylation. This residue has been proposed to have a role in the regulation of p53 protein stability. p53S312A/S312A knock-in mice are viable, fertile and not –pre-disposed to spontaneous tumor formation. In addition, the p53S312A protein was found to be activated as efficiently as wild-type p53 and its turnover rate was not affected, suggesting that despite in vitro evidence this phosphorylation event may not be critical for in vivo suppressive functions.

Let’s get some of the terms out of the way. “Phosphorylation”, “acetylation”, and “sumoylation” all refer to the addition of certain chemical groups (such as phosphates) to the protein – it’s basically attaching stuff to p53. “In vitro” pretty much refers to the testing of cells in a test tube (or Petri dish, or whathaveyou) whereas “in vivo” refers to testing done on whole organisms. “Sabapathy” is a person, not a biological term. “Knock-in” refers to a type of genetic engineering. “Wild type” means the default protein, or the protein as it “normally” would appear, unmutated. (I’ve always found the term counter-intuitive.)

Now, presuming anyone is still with me here, the important aspect of the above excerpt is where it says, “In addition, the p53S312A protein was found to be activated as efficiently as wild-type p53 and its turnover rate was not affected, suggesting that despite in vitro evidence this phosphorylation event may not be critical for in vivo suppressive functions.” In other words, the genetically altered ‘test tube’ results showed that the addition of a chemical group was important, but further evidence showed otherwise. One thing this means, as all scientists know, is that we ought not jump the gun.

Another way to think of these results is to compare red hots dogs and apples. Each one is known to contain nitrites, which is a chemical compound linked to cancer. However, whereas red hot dogs have a small connection to tumor development, apples have no connection. Why? There is a complex interaction between meat and nitrites which results in the production of the actual carcinogenic compound. Apples, on the other hand, even if they did interact with other chemicals (probably ones within the body), have components which would help the immune system and thus help prevent cancer, at least to some degree. Or to use another comparison, tobacco cigarettes and marijuana contain a ton of carcinogens, but only one (cigarettes) has a causative link to cancer. Presumably some other chemical(s) in marijuana counteracts the carcinogens. But however the cancer is prevented, it happens through a complex interaction that needs to be studied. Lab results are wonderful and they’re a major reason why we live so healthy and so long today, but they aren’t the final word. In fact, we ought not think of anything within biology as being the final word. We have large scale statistical results that will be true in virtually all cases, but there are no hard and fast rules for how organisms will interact with their environments. We need to test and test and test – and science will always do that – but the real solution here is that we need to be sure we aren’t jumping the gun. After all, no one wants to be a quack.

Filed under: Biology | Tagged: cancer, Cigarettes, Hot dogs, Marijuana, Nitrites, p53, Quacks, Tumor suppression | 1 Comment »