Inching Toward Alchemy

Although materials scientists and atomic physicists don’t devote much time to the study of nuclear transmutation—that is, attempting to convert base metals into precious metals—achieving another objective of alchemy is getting closer each day. The products of modern pharmacology are what alchemists would have thought of as magic potions, and indeed, with every paper published on the synthesis of new drugs, the structure of proteins, or gene expression, we inch towards the goal of being able to cure yet another disease or sickness. A relatively recent breakthrough in molecular biology has captured the interest of the pharmaceutical industry and researchers alike and promises to lead pharmacology into the next several decades.

The breakthrough, which came only about ten years ago, is RNA interference. RNAi, as it’s called, is a system within living cells that helps control which genes are active and how active they are. “RNA” refers to a type of molecule, similar in structure to DNA, that facilitates various cellular processes including the synthesis of proteins and the regulation of gene expression. “Interference” refers to a function of this particular type of RNA, which is, generally, to “interfere” with gene expression.

To understand why RNAi research is so promising, a bit of historical context is helpful. In the late 1980s, a group of researchers led by molecular geneticist Richard Jorgensen was working on trying to alter pigmentation in petunias. Their hypothesis was that if they were to add additional copies of the gene responsible for flower pigmentation, the resulting petunias would have more intense color. What they found instead was that the petunias with the extra pigmentation genes had no pigmentation. This was a strange result. The researchers took a closer look at the modified petunias and discovered that their attempts at increasing the expression of the pigment gene were counteracted by something else in the petunia cells. The question was what that something else was.

The answer to this problem came out of a decade of hard work on a completely different organism—the nematode. As it turned out, Jorgensen’s group had stumbled upon a defense mechanism in living cells that no one had yet discovered. When they tried to over-express the gene for pigmentation, they had triggered the defense mechanism, which, when it found proteins made by the altered copies of the pigmentation gene, destroyed every protein produced by that gene. As a result, the petunias ended up completely white. The defense mechanism was interfering with gene expression, and it was dubbed RNAi.

Researchers soon thought to use RNAi to their benefit. The idea, roughly, was to over-express undesirable genes in unhealthy cells in order to trigger RNAi to get rid of them. As it turns out, RNAi already plays an important role in helping cells defend against viruses, which spread by attaching to healthy cells, depositing their own RNA, and forcing the cell to make viral proteins. RNAi can be made to attack viral RNA and effectively “cure” the cell.

A number of Columbia University scientists have done extensive research using RNAi. Dr. Oliver Hobert at the department of Biochemistry and Molecular Biophysics at the Columbia University Medical Center uses RNAi techniques in the nematode to identify the genes that maintain the complicated and highly specific nervous system network. Dr. Brent Stockwell in the downtown campus’s biology department researches the ability of RNAi to change the ways cells respond to cancerous signals and neurodegeneration. His group’s screens are targeted at the identification of specific genes that play a pivotal role in cellular disease mechanisms.

RNAi is promising. In the words of Nobel Laureate Phillip Sharp, “RNAi is the most important and exciting breakthrough of the last decade, perhaps multiple decades.” Indeed, we have already seen incredible progress in the use of RNAi to cure disease—five years ago, a Stanford-based study headed by Anton McCaffrey found that the Hepatitis B virus could be inhibited in mice using RNAi and a year later, a team at the University of Iowa published results that suggested that RNAi could help fight Huntington’s disease. RNAi is truly medical alchemy.

Adrian Haimovich is a junior in the school of Engineering and Applied Science majoring in applied mathematics. Vedant Misra is a Columbia College senior majoring in physics and mathematics. Nova runs alternate Wednesdays. opinion@columbiaspectator.com