Saturday, March 24, 2012

Ten commandments in modern societies -5

"Keep in mind that everybody is a mutant!"

No, this is not about the X-men.  No, this is not the same as "We all have sins" or "Nobody is perfect", cliches that are void of real meanings but help make excuses. And it is not about people being different.  We can be different, like in skin colors or blood types, but certainly still normal in those aspects.

This fifth commandment has a long line of solid scientific findings backing it up.  While we'd like to think that bad things, like AIDS, cancers, accidents, happen to everybody but ourselves, the reality is that bad things are of equal opportunities.  If there is an angel, or a model human genome with every nucleotide of its DNA is "perfect", and if we compare our genomes to it, we will find none of us is as good.  A recent paper provides the most evidence thus far: A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes, 2012 Science 335: 823-828.  They found that all the sequenced human genomes contain a large number of variants that are predicted to inactivate protein-encoding genes.  On average, every person has ~ 20 genes (out of ~ 20,000 in total) that are completely inactivated.  If we look at the many known mechanisms that can kill gene expression beyond the DNA level, the list of "dead" genes is likely much higher.  There is no wonder that more and more medical problems are being discovered and the incidents of known diseases are going up, as our knowledge and technical tools are getting better and better.

What can we do about it?  This is the real question, because for various reasons we can't simply correct our DNA mistakes easily or early enough.  We just have to accept the fact that we all have specific problems others don't, and that such problems are mostly due to genetics beyond our control.  Luckily, most problems are minor and appear in only limited situations.  But genetics goes a long way to explain why everybody behaves in an idiosyncratic way, consciously and subconsciously.

Genetics not only influences individuals, it also affects societies, simply ensembles of people and many genomes.  Societies determine to a large extent how individuals see things and think.   So to take this commandment to a higher level, every society is also a mutant, even if not entirely due to genetics.  Many things in a society are not "perfect", including rules that have been around for thousands of years.

As a corollary, be critical towards ourselves and towards the societies.  Don't take anything for granted.  And we have to constantly and actively suppress the effects of mutant genes and their consequences.  Just like an HIV-infected patient.  The current treatment suppresses but does not eliminate the virus, and you need to take the pills consistently.  For many of the ills at the individual and societal levels, we have to do the same.  A glaring example is racism.  Everybody has racist tendency, because it is simply rooted in evolution.  All organisms like to be around the alike, wolves, horses, etc.  Human ancestors needed to group together to fight wild animals as well as other tribes.  This was how friends and foes are recognized for billions of years.  In modern societies human skin color is no longer defining friends and foes or good and bad, but part of our genes and brains are still wired to such and other prejudices.  This is something one needs to actively fight to suppress every day, no matter he is white, black, yellow, or brown.  Very often we see people violate this "rule".  It is likely because they forget to take their HIV pills.

As the last note, the skin color in some societies still predicts economic status.  Who doesn't want to be that gorgeous person with well-tailored dress and designer shoes riding in expensive cars to dine at fancy restaurants?  Such a person is also often perceived to be nobler than a poor guy.  Here is an interesting paper looking at the morality of people of different social classes: Higher social class predicts increased unethical behavior, 2012, PNAS 109: 4086-4091.  In essence, with numerous tests and real, hard data, this paper demonstrates that upper-class individuals are more likely to break the law or engage in unethical acts than the lower-class individuals, given the same chances.  Don't paint everybody with a big brush, but we do need to think what lies beneath the glamorous looks.  Because judging a person by his look or outside attributes is also a common human fallacy.


Wednesday, March 7, 2012

How good is your science?

Science (including technology) is the most meaningful activity people can perform after survival.  This says a lot, ranking it ahead of politics, financing, certainly arts, sports, and entertainment.  

The manner scientific research is run these days is so much different from the Newton's time, even Einstein's.  Many more people are doing it, and much more money is involved.  This change parallels with basically everything else in the world.  But a central question remains: is what you are doing significant, useful, or any other descriptive?  Are you any good?

There is always a need to evaluate, but not always a right tool to do so.  If you have a lot of grant money, perhaps you are good.  If you publish in Science the journal, perhaps you are good.  If your company sell for a lot of money, perhaps you are good.  But these criteria do not directly address the virtue of your science.  Perhaps you are just good at marketing or just have some powerful friends.

As a point to illustrate that scientists are as morally feeble as everybody else, to evaluate grants and people these days, even though nobody respectable dares to say aloud he counts journals' impact factors (IF), and everybody respectable says he does not, this is essentially what every review group does and does only in the world.  A less common number to look at is citation.  Citation has its own problem as well, for it differs amongst fields.  But at least a higher number means more people remember it.  Unfortunately, people also often remember wrong; omission and citing the wrong papers is common.

A simple way to rank what scientists do actually is to use a stamp collecting and door/room analogy.  Nature makes and places many stamps in many places (rooms).  So what we are producing or publishing in journals is collecting stamps.  Most stamps are very boring and not that important despite what we'd like to claim.  Or similar ones have been collected by others before, and you simply find extras in the same or a slightly different place later.  The often "me, too" science. 

Great scientists obviously collect the most important stamps, but they accomplish it usually not by out-competing others for stamps in the open, but by finding and opening a door to a new room(s) with unknown stamps.  The mere fact of finding a new room, or more specifically, proposing a brand new idea, pointing out a new area of research, or developing a new technique, is often much more important than picking up the actual stamps themselves. 

For example, Newton's contributions to physics (ideas) and math (tools) have been applied in basically every aspect of life since 1700s.  Darwin's idea was so profound that it gave us the best and most comprehensive understanding of life and diversity.

So how good your science is depends ultimately on how widely applicable your new knowledge is.  The more rooms your singular discovery finds, the more doors it opens, the more significant it is.  Like you propose a formula E=mc2 or a mechanism that is universal in every particle or biological system.  If the mechanism you show is valid in every cell in a human body, then it is more important than if only in, say, a neuron.  Even if the latter might be used to combat dementia, the former might be used to target many other diseases, besides neurological disorders.  Another example is developing a model that people then use to answer a wide range of questions that have been difficult to study before, like yeast, flies, and worms.  Or a technique that over 95% of the biologists will use at least once in their career.  It is certainly possible that a lesser (still good) discovery can net you much more money, like NO and Viagra, vs Mendel's laws or the DNA double-helix model, but anybody will know which is more important scientifically. 

Of course, some examples listed above are truly the best of the best.  And not every single work of the great minds has been of supreme importance.  Some Nobel Prizes were awarded just for collecting good-looking stamps.  In fact, most work by everybody, even the greatest ones, is quite banal, so everybody is "guilty".  Even papers in the "best" journals are >90% stamp collecting to a higher power: more sequences from different species/cells/different conditions, the same mechanism repeated in a different system, albeit perhaps more related to human diseases, or the same old pathway for a sexy protein or RNA.  It is still a bad idea to undervalue knowledge, no matter how useless it seems initially.  For every Pete Sampras, we have Patrick Rafter, Tommy Haas, and many others.

But you will be guiltier if you never go beyond the unimaginative even when it guarantees publications and grants under the current environment, which is the reality.  After all, Darwin did spend years collecting stamps (specimens), but then he came up with the idea and had all the data to back it up.