Speculation Press - Weird Science

We will put up a new Weird Science page on an irregular basis. Why do we have a section on weird science? For our visitors' enjoyment and edification. And because we love discussing cutting-edge technology. Most of the weird sciences will be biologically-based, because that’s what we know best.

The author of the Weird Sciences pages is Winifred Halsey, President of Techknowledge Research.

To read past Weird Science pages, please visit our archives.

BIOCHIPS – A NEW DIAGNOSTIC & RESEARCH TOOL

Anyone who watches new technologies, particularly in biotechnology, knows about biochips, which combine semiconductor technology with molecular biology.

What is a biochip?

Biochips are similar to semiconductors, except that instead of having electronic circuits, they have biological material, DNA or RNA or protein, attached to the surface of a "chip," which can be glass, plastic or silicon.

There are two main types of biochips, depending on the material attached. Nucleic acid biochips, which have DNA or RNA, and protein biochips. There is another type of biochip, called a lab chip, which uses microfluidics to do many of the standard lab tests that are run in hospitals today. We won’t go into that type of chip as it normally is just a miniaturized version of standard clinical chemistry tests, and it doesn’t necessarily have a biological component.

Science Background on Biochips

Deoxyribonucleic acid, DNA, contains all the necessary instructions for all living organisms, except a few viruses, which are RNA based. DNA is double-stranded, and contains a nucleoside base (adenine, cytosine, guanine or thymine), a ribose sugar and a phosphate group. James Watson and Francis Crick, in 1953, discovered that the DNA was arranged in tightly twisted into double helix. DNA is grouped together as genes, although the grouping may not be directly adjacent.

DNA (genes) are differentially expressed, meaning that most of the time the majority of the DNA is silent, or unexpressed, by being tightly twisted together. But when a particular section of DNA is needed, it is expressed, or unwound so that the DNA can be read and the appropriate proteins made. This is done by copying the DNA’s instructions to RNA, specifcally messenger RNA (mRNA). This process is called transcription. The mRNA then translates the DNA "message" into protein. This process is summarized below:

DNA transcription \ mRNA translation \ protiens

Biochips are used to identify unknown DNA or RNA (nucleic acid strand) via the process of hybridization—or bonding—between an unknown nucleic acid strand and a known nucleic acid strand.

This is done by first denaturing the unknown DNA with heat, which melts the bonds between the two strands of DNA, producing single-stranded DNA. Then the unknown DNA or RNA is washed over a biochip, which has single-stranded DNA or RNA affixed to its surface. If one of the pieces of DNA, or RNA on the biochip is complementary (matches) to the unknown DNA / RNA, then hybridization will occur and a fluorescence is given off that lets a researcher know the DNA or RNA matched the unknown DNA.

A graphic overview of a biochip:

Uses for Biochips

There are six potential markets for biochips: 1) pharmaceutical research; 2) medical diagnostics; 3) forensics; 4) transplantation; 5) identity testing; 6) water and environmental testing.

Biochips and Pharmaceutical Research
Currently pharmaceutical research is the only market for biochips. They are being used to discover new drugs and in research into functional genomics.

In new drug research, biochips are used in drug assays and in toxicology, where the biochips can test the toxicity of new drugs so that fewer, or perhaps eventually, no animal testing needs to be done.

Functional genomics is the area where biochips are being most widely used. Nucleic acid chips are being used to identify which genes are active during specific disease states, and which ones are active in normal tissue. This information tells researchers which genes are responsible for specific diseases. Ultimately this sort of research can lead to personalized medicine, or pharmacogenomics. (See previous Weird Science)

Biochips and Disease Diagnostics
Biochips are being tested now for two different uses in disease diagnostics: 1) identification of infecting microorganisms at the genetic level; 2) categorization of cancers at the genetic and molecular level.

It is postulated that at some point in the future, if a person, or animal, becomes sick with a microbial infection, they will go to the doctor office where a genetic analysis will be done on the infecting bacteria. The doctor will know, within an hour, exactly what the infecting organism is, and exactly what antibiotic, at what level, will kill it. No more hit-and-miss guesses as to what is the best antibiotic at what dosage.

In the same way bacteria and other infecting organisms can be genetically analyzed, so too can cancers. Currently cancers are broadly typed as adenocarcinoma, small cell cancer, etc. Such broad categories help provide guidelines for treatment, but don’t provide any precise answers. There are many different types of adenocarcinoma—ovarian, prostrate, etc. They each react differently to different therapies. Even within a single type, such as ovarian, all cases do not response equally to a specific therapy. But if cancers could be categorized at the genetic level, then the doctor would know exactly what therapies would have the best chance for success.

Currently, biochips can’t be used for disease diagnostics because they haven’t been cleared by the FDA. It will probably be several years, at least, before they can be used regularly for disease diagnostics, but the time will come.

Biochips and Forensics
DNA testing in high profile criminal cases has been on the news quite a bit over the last few years. DNA testing is the gold standard for determining guilt or innocence of a suspect. At this point, DNA testing involves the analysis of DNA that has been chopped up with enzymes. The process usually takes, at best, a couple of weeks, and there is always concern of DNA cross-contamination at the testing facility, or within the police evidence room. DNA-based biochips could provide DNA analysis right at a crime scene. There would be less delay and less handling of the material with less potential for errors and contamination.

Biochips and Transplantation
DNA- or protein-based biochips could be used to more precisely match donors and recipients to lessen rejection of transplanted organs.

Biochips and Identity Testing
DNA-based biochips could be used for identity testing, including parental identity testing, genealogy, and refugee testing.

Biochips in Water and Environmental Testing
Some of Affymetrix’s biochips are already being used to test the water supply in Atlanta, Georgia. Biochips are a natural for on-the-spot testing for bacteria or pesticide contaminants in water or even in the air. Biochips are being used as part of the Department of Defense’s biological warfare response.

Market for Biochips

A recent research report by Bioinsights, quoted in Electronic Business, April 2000, gives the following market for biochips, in millions of US dollars:

Year	DNA Chip	Lab Chip	Protein Chip	Total
1999	$158	$14	$4	$176
2001	$249	$35	$8	$292
2005	$745	$157	$68	$950

Companies Working in the Field

The market leader in biochips is Affymetrix, a company that was spun-off of Affymax, a combinatorial chemistry company, when Affymax was bought by Glaxo Wellcome in 1995. Affymetrix is the only company with commercially available biochips, although many other companies are close to commercialization having beta-test products in the field.

Other companies working exclusively in biochips include: Nanogen, Hyseq, Genometrix, Synteni (now owned by Incyte), Oxford Gene Technology, Visible Genetics and Vysis. These are just the best known of the companies. Because of the large potential of biochips, new companies pop up every month. A well known research supplier, Amersham Pharmacia Biotech has developed biochips for the research market.

Some large, well-known electronic companies are also working in this field, including Motorola, Hitachi and Samsung.

Future of Biochips

Much of the technology that is currently used to manufacture and analyze the results of biochips is labor intensive and expensive. Better methods of manufacture and detection are being developed, including direct detection of hybrization by electric current, based on the fact that single-stranded DNA conducts electrons at a different rate than double- stranded DNA.

For all of its minor drawbacks now, biochips are an enabling technology of the future. They will become part of all of our lives. There will come a time when it will be as difficult to remember life without biochips as it is to imagine the TVs with vacuum tubes.