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Author: edawg8 Old School Fool Add to my Favorite Fools Ignore this person (you won't see their posts anymore) Number: of 24974  
Subject: The Little Biotech FAQ, v.1 Date: 1/5/2000 6:20 PM
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In light of the need for more information and understanding of the biotech sector, I propose the creation of a common FAQ to act as a convenient repository of knowledge for us biotech fools to use. I don't know about my fellow fools, but I for one feel like I just don't have time to follow every single thread on numerous individual company boards, and would really like a thorough overview of the sector to put everything into perspective. I contend that, as we understand this sector better as individuals, we can more intelligently discuss the issues, as well as perform better research as we muck around for info on our favorite companies. The end result is that we all benefit; how well we cooperate and share information will determine the degree of benefit.

I also propose that it should be updated every once in a while to remain accurate and timely -- whoever's updating it should retain the contents of the previous versions of the FAQ except where the information is incorrect, and credit should be granted to its contributors.

Okay, someone's gotta start this thing, so I might as well give it a shot...

GENOMICS COMPANIES

Note: you can scroll down to the Genetics Concepts section if you need some clarification.

Q. What's the scoop on these genomics companies? Who are the players?

A. I've heard of Human Genome Sciences (HGSI), Incyte Pharmaceuticals (INCY), Millenium Pharmaceuticals (MLNM), Genome Therapeutics (GENE), Genentech (DNA), Celera Genomics (CRA), Gene Logic (GLGC), Myriad Genetics (MYGN), Genset (GENXY), PE Biosystems (PEB), Affymetrix (AFFX). Fellow fools can add to this list for subsequent versions of the FAQ.

Q. What do they do?

A. You can take a look at their company briefs by clicking their links below:

HGSI: http://moneycentral.msn.com/investor/research/profile.asp?Symbol=hgsi&iPage=qd
http://boards.fool.com/Message.asp?id=1130088000055000&sort=postdate
(this is Elric Seven's post of the Fools' HGSI Tour)

INCY: http://moneycentral.msn.com/investor/research/profile.asp?Symbol=incy&iPage=qd

MLNM: http://moneycentral.msn.com/investor/research/profile.asp?Symbol=mlnm&iPage=qd

GENE:
http://moneycentral.msn.com/investor/research/profile.asp?Symbol=gene&iPage=qd

DNA: http://moneycentral.msn.com/investor/research/profile.asp?Symbol=dna&iPage=qd

CRA: http://moneycentral.msn.com/investor/research/profile.asp?Symbol=cra&iPage=qd

GLGC: http://moneycentral.msn.com/investor/research/profile.asp?Symbol=glgc&iPage=qd

MYGN: http://moneycentral.msn.com/investor/research/profile.asp?Symbol=mygn&iPage=qd

GENXY: http://moneycentral.msn.com/investor/research/profile.asp?Symbol=genxy&iPage=qd

PEB: http://moneycentral.msn.com/investor/research/profile.asp?Symbol=peb&iPage=qd

AFFX: http://moneycentral.msn.com/investor/research/profile.asp?Symbol=affx&iPage=qd

Q. What about this race between HGSI and CRA to sequence the entire genome?

A. I've heard more than a few people get the company Human Genome Sciences (HGSI) confused with Celera and the government sponsored Human Genome Project (HGP). This could be due to slightly misleading information found in two articles:

1. The otherwise excellent Buy Report article on CRA from the RuleBreaker port, near the end of the 1st Rule: Top Dog or First Mover in an important, emerging industry, section, says "As soon as Celera was born, HGSI increased its intentions regarding its mapping of the genome." This undoubtedly should read HGP, instead of HGSI.
http://www.fool.com/portfolios/rulebreaker/trades/rulebreakertrade_cra991216.htm

2. The otherwise excellent Individual Investor article on genomics stocks, says "Unlike companies such as Human Genome and Celera Genomics, which are hastily mapping the entire DNA sequence..."

http://www.individualinvestor.com/tbd/anfdt_frm.asp?ff_id=3934

Okay, for the record, Human Genome Sciences (HGSI) has nothing to do with either the Human Genome Project (HGP) or Celera. HGSI is not in the business of sequencing the entire genome. Celera and the HGP are. HGSI is all about discovering and sequencing individual genes and using them to make drugs, growth factors, and signalling molecules.

GENETICS CONCEPTS

Q. Gene, genome, chromosome, DNA, base pairs? What's the difference?

A. Here's how I understand it. For you molecular biologists and geneticists out there, if there's something wrong, tell us so it can be corrected for the next version of the FAQ.

Let's use the common encyclopedia analogy to help us. Although this is far from a scientific analogy, it's easier to understand like this...

1. A gene would be represented by an individual article on something, e.g., the light bulb. You want to know how a light bulb works, you read it. In a similar way, the hair color gene, for example, contains the instructions on how to build hair of a specific color.

2. A chromosome would be like a single volume out of the encylcopedia set, e.g., Volume 6, F-G. All the articles that begin with the letter F or G would be in this volume. Similarly, chromosome 6 would have a whole bunch of genes on it (what genes are there and what they do is what the scientists are trying to find out).

3. The genome would be like the entire encyclopedia set, which, for us contains 14,000 articles (genes) in 46 volumes (chromosomes). Genome refers to the entire genetic code of a species (e.g., human genome, drosophila/fruit fly genome, H.influenzae genome).

4. DNA would be represented by the patterns of ink and paper of the encyclopedia. It is what genes are made out of, much like articles are comprised of a whole bunch of different patterns of ink printed on a sheet of paper. Don't get wrapped up thinking what DNA does -- it does nothing. It's simply the material that genes are made out of. It's just like saying what is this desk made out of? Wood. What is the encyclopedia made out of? Nothing more than ink and paper. And the human genome? Yeah, it's made out of DNA.

5. Base pairs are like specific patterns of ink. For example, a straight line up and down represents the letter l, and a circle pattern represents the letter o. So, a base is like a letter. But with humans, there are only 4 "letters" in that genetic alphabet: A, C, T, and G. Strangely enough, they make enough words, sentences, and paragraphs for a whole bunch of articles on everything from hair color to body weight. As for bases being "paired", don't worry about that for now. It will just confuse you.

Q. What about amino acids, proteins, cDNA, mRNA, ribosomes, etc.?

A. Okay, so you got a bunch of genes. These genes contain instructions or messages that must be expressed eventually as proteins. These proteins essentially carry out the instructions encoded in the genes. A whole series of steps occur before a gene is expressed as a protein, though.

Let's use an analogy here of music being recorded from a CD onto a tape, and then being played back in a walkman...

Let's say a CD is just like a chromosome. It's got a whole bunch of tracks on it just like a chromosome has a whole bunch of genes on it. But say for some reason that you can't actually listen to music off a CD. It must be recorded onto tape before you can listen to it on your walkman. In much the same way, information encoded in your genes cannot be read directly by the body. A gene must first be transcribed into messenger RNA (mRNA) (imagine that the mRNA is like a song recorded onto tape) with the help of transcription factors and polymerase enzymes (let's say TF's and polymerases are like the CD player and tape recorder -- they read the information off the CD and record it onto tape). mRNA makes its way out of the cell's nucleus (where all the genes are stored, like a CD collection) and is translated into protein 3 bases at a time by a ribosome. With the CD/tape analogy, let's say that it's like taking the tape out of the tape recorder, putting it into your walkman, and pressing play. Each trio of bases (e.g., ACG) is called a codon. As the codons pass through the ribosome in sequence, a transfer RNA molecule carrying a specific amino acid on its back links up with its respective codon, forming a chain of amino acids. This is like the music recorded on the tape being picked up by the head on the walkman. The head translates the information on the tape into an electrical signal that causes the headphones to produce music. Each codon calls for a specific amino acid to be attached onto the chain until the gene's instructions are fully expressed in the form of a protein. (proteins are simply a chain of amino acids twisted and folded in a specific shape) The protein that is produced is the expression of the gene's instructions, much like the music you hear is the ultimate expression of the stuff recorded on the original CD.

GENETIC CONCEPTS APPLIED TO GENOMIC COMPANIES

Q. Okay, so what's all this fuss about HGSI and all those other companies like that who are studying individual genes as opposed to companies like Celera and the government's HGP who are studying the entire human genome?

A. Ah, here's an interesting question.

1. Let's depict graphically (HA!) the relationship between a gene and the genome:

<----+++++---++++---+++++++++---++-----++++++--+-->
<-++---++-++++--+++++---------+++-----+++----->

Each <---++++----++--> line as you see above represents a strand of DNA. The genes are represented by blocks of ++++'s. The --- represents sections of DNA with no genes on it. Let's use a mapmaking analogy...

Genes would represent cities and towns... civilization. The blank spaces in between would represent the countryside or back woods where nobody lives...

Suppose you have a atlas of the world. You see continents, oceans, countries, states, provinces, and local regions. You know where everything is in relation to each other. If you were in a plane, and you were flying from New York to Boston, you could use the latitude and longitude to determine their locations, you might see some landmarks like rivers and mountains to guide you, other cities and towns in the area, etc. You know where those cities are in relation to one another, you know where they are in terms of the country, and you know where they are in the world. That is the point of sequencing and mapping the entire genome. It's like you're surveying the entire globe.

Now discovering and sequencing for genes on the other hand is rather like looking at a single city and making a map of just New York, or just Boston. You got every block of the city covered, though, in great detail. And some of those companies are trying to do more than just make city maps. They're trying to make tourist guides, restaurant reviews, etc. Essentially, they're trying to find the what characteristics each gene has as well -- what proteins they produce, what they do, how they are activated, etc.

Knowing everything about individual cities is one thing; knowing the general overview of the entire earth is another. But would you say one type of information is more important than the other? On one hand, you know everything about certain cities. But, assuming you have a stack of city maps, you still wouldn't know much about where they are in relation to each other, or in terms of their exact location on the earth. The flip side is that you have the broad overview of the entire planet with all the cities represented as little dots on the page, but you don't really know enough about the cities themselves.

So you have companies like HGSI, INCY, and others that are in the city mapmaking business, and you have CRA in the atlas or globe making business.

At the moment, it seems like city mapmaking is more useful, in that genes are the functional parts of the genome -- they are the parts of the genome that create functional (or dysfunctional) proteins that carry out the instructions of our genetic code. e.g., if we found that a certain gene was responsible for obesity, we could isolate and sequence it so we could produce a drug that could be taken by people with a defective obesity gene. Actually, we already have done that. It's called the leptin gene.

However, we would still like to know the big picture. People still buy both city maps and atlases. For example, where are these genes located? The American Midwest? The south of France? This kind of information would seem to be useful for medical diagnosis in the future. Imagine that the human genome is finally sequenced and mapped in its entirety. And imagine that they will have the ability to sequence your own personal genomic map. It could be part of everyone's medical chart in a decade. If you come into the doctor's office and say I'm not feeling well, the doctor could simply look at your genomic map and say "AHA! You have disease X. Let's book you for gene therapy next week."

Q. Where can I get more info?

A. Here are some useful links on:

Genetic Concepts
http://vector.cshl.org/dnaftb/asp/splashtable.asp

HGSI vs. HGP and Celera post
http://boards.fool.com/Message.asp?id=1020007000462005&sort=postdate

US News article on HGP vs. Celera (Jan 2000)
http://www.usnews.com/usnews/issue/000103/genome.htm

Time Magazine article on Biotech and Genetics/Genomics
http://www.pathfinder.com/time/magazine/toc/0,3392,1101990111,00.html

The very excellent issue of Time may be a bit dated (Jan 1999), but it not only talks about the HGP, CRA, and the genetics/genomics industry in general, but also talks about the ethical questions that could haunt this sector in a couple years when the mainstream press starts sensationalizing the ethical issues of whether it's right or wrong, should we be playing God, etc.? You remember the small uproar when Dolly the sheep was cloned, right? It could be much worse when the human genome is mapped. What will happen to the genomics stocks? There's an issue to think about for my fellow Fools.

And don't forget to read the Buy Report on CRA for the RuleBreaker portfolio and the Individual Investor Genomics Stocks article (links near beginning of FAQ)
_________________________

Well, that's it for now. To the experts out there, please reply with corrections, comments, and suggestions where you see fit. For example, are those analogies clear or are they confusing? If there are other questions and answers that you think should be included, bring them up. Better yet, if anyone feels inclined to improve upon this FAQ by taking into account community suggestions, editing errors, and adding content, and thereby wishes to create a revised version, please do so! Your efforts will be appreciated by your fellow fools.
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