Celera Completes Human Genome. Sorta.
kovacsp was the first to write to us about the announcement from Celera that they had completed mapping of the human genome. Note: This is /not/ the be-all, end-all. They have finished *mapping* one person's genes. With Celera's approach, this means that they now need to being assembling the information they've gathered. All in all, Celera plans to do the same process with four other people. The Human Genome Project, using a more traditional approach is still a couple years away, but the race is still pretty close.
Or new laws (like current blood test laws) will now check DNA and say you can't marry [SO] because your children will be at risk for [condition].
Where does it end?
Looks like that hell-spawned Clinton better make his move soon, the clock's ticking on his reign as "God?". Or is Al Gore, father of the internet, truly the antichrist? Isn't it sad what living under power lines can do to a person?
I am not a biologist...yet (bio undergrad though)
The problem is that we ALL have recessive detrimental genes. It has been shown experimentally (see Dobzhansky's work with D. melanogaster) that it only takes a relatively small amount of inbreeding to significantly raise the chances of offspring inheriting lethal genotypes and have severe viability problems. That's why inbreeding is so avoided in much of the animal kingdom (well, that's not true either, as many species keep SOME level of inbreeding to ensure the inheritance of evolved gene "blocks" of genes what work well when inherited & expressed together, but for most mammals significant inbreeding is avoided)
Sincerely,
Kevin Christie
kwchri@wm.edu
Yep. Celera's approach is somewhat akin to the following:
/ newsid%5F677000/677815.stm
1) Take a 5 copies of a HUGE book.
2) cut out random sections of 500 words each.
3) thoroughly mix the pieces.
3b) Lose several of the pieces.
4) add mistakes to the pieces
5) Attempt to reassemble to book based on the overlap between the random pieces of 500 words each.
Notice that the missing pieces and mistakes will make it quite difficult to reassemble to book, even though you have redundant pieces.
What I described above is also a far cry from the billions of base pairs in the human DNA "book".
The exact details are above, of course. Celera is slick, but they are just boasting at the moment.
another good link:
BBC report on Bill & Tony requesting the human genome be in the public domain:
http://news2.thls.bbc.co.uk/hi/english/sci/tech
Celera will provide data from its own databases, via tools it sells for the job.
Other companies can then patent particular sequences as they apply to a particular discovery. For instance, Incyte could patent the knowledge that a given sequence causes colon cancer, or AIDS.
Nobody can (yet) patent a sequence itself - nobody is even lobbying for this.
Incyte is, OTOH, still going ahead with their own sequencing of the human genome, AFAIK.
I'm responding to something marked "Funny", but actually there are real applications for DNA compression. For example, exons are less compressable than introns. This could have applications in gene finding (Sequencing genomes just gives you a series of bases, gene finding programs help interpret the sequence by finding areas that encode proteins)
According to a friend of mine at the Whitehead Institute at MIT, which is part of the HGP, Celera has sequenced the data from one person, not assembled it. To have all the data sequenced is the equivalent of having every character from the source files for the linux kernel, but not knowing what order they are in.
HGP as of mid March had completely sequenced and assembled 2/3 of the genome, based on 6 individuals. Current amount complete is closer to 75%.
This really trashes Celera's business plan, which as far as I know is to sell the sequenced data to companies like Amgen for them to assemble and profit from. At least 2/3 of the information is already available gratis, already assembled.
Of course, this also makes Celera's work easier, since it can use the 2/3 of assembled data as a backbone against which to assemble the remaining third. But by the time they finish that, how much more will the HGP have published.
Never send anything unencrypted that you don't want to have appear in court.
Wouldn't that cease and desist letter come from the Law Firm of Mephisto, Asmodeus, and Beelzebub instead? :^)
I've finally had it: until slashdot gets article moderation, I am not coming back.
> Your dad could be Michael Jordan, but if all you do is sit at your computer and eat junk food you won't make the NBA
;)
No, but if you were a clone of Michael Jordan, it's unlikely you would be inclined to sit at your computer and eat junk food all day. 'course a butterfly flapping its wings in zimbabwe might cause a tree to fall on you sometime, leaving you in a wheelchair, unable to get in the NBA. pesky butterflies, always causing disasters
I've finally had it: until slashdot gets article moderation, I am not coming back.
Doubt it. Couples nowadays don't (usually) give birth to identical children, despite the chromosomes of the mom and dad remaining unchanged. Of course, there is always The Milkman theory of species diversification, but I tend to think that every sperm or egg contain unique genetic information even within a single individual (or however that should best be said, you know what I mean...)
Work is for people who lack the imagination to play.
90% percent of our genes are similar,
probably because we shared 90% of our evolutionary
history (first 3.5 of 4 billion years).
Most of these similarities are basic proteins
all land animals share in their metabolism.
Celera is using five, while the NIH/DOE project
is using ten. 995 out of a 1000 base pairs
will be the same between humans. The fifteen
humans will provide error-cross checking,
plus the locations where humans vary.
The published genetic codes are ati ?db=Genome> this government site </A>.
<A HREF=http://www.ncbi.nlm.nih.gov/entrez/query.fcg
Submission of data to this site is REQUIRED
before a scientific journal will publish an
article about your results.
However, these may not appear on the web site
until the day of publication (e.g. the fly genome in March 24, 2000 Science).
So I wouldn't look for the Full Human until
sometime in year 2001 here. (The shortest chromosome #22 is all there already.)
Human relatives differ by 0.1% or less.
Humans different by 0.5% among themelves.
Chimps differ from humans 2.0%.
Fruit flies differ by 10-15%.
Most of the human cancer gene defects have been
found in fruit flies according to March 24 Science article.
In the Fly sequencing description, they split
each chromosome into three different size pieces-
about 2K, 10K and 100K kilobases.
Then they do mutual comparisons of ends to find
overlaps, sort of like a "super grep".
The pairwise comparisons runs into the trillions,
hence supercomputing.
Matching "junk DNA" pieces is difficult,
because junk DNA tends to be very repetative.
They've been getting a 98% match rate.
These assembly tricks are described in detail
in the March 24, 2000 issue of Science.
The human genome is 15 times larger than the fly genome.
This ethod has been tested on several smaller
organisms with surprising success.
But weren't as resourceful as the private section.
They were planning for take 15 years and $3 billion.
Mr. Ventor figured out how to do it in three years
for 1/10th the price.
I read somewhere last year about President Clinton ....
:-) :-)
donating DNA
:-)
This story has been up for a few hours, and nobody has said anything stupid about processing the genome on distributed.net yet. :)
Comparing this:- All in all, Celera plans to do the same process with four other people. to this: - The three million fly fragments are sampled from the gene-rich regions of the genome (about 120 million letters). For a simple genome there is a larger sampling, but for a more complex creature there is a smaller sampling. Doesn't this seem a bit of an oversight? OK, you might be able to improve your processes, but this doesn't seem to scale. Much like quickly typing nonsense in an attempt to grab that elusive first post...
Patents are for inventions, not discoveries. If you patent something that you didn't really invent (e.g. a genome, even the one that you happen to use) and try to enforce it, you should lose.
Hmm.. but can a pair of parents copyright their child's genome? It's most likely a unique expression, and an argument could be made that they did really create it, even if they had no conscious control over the details. Hm.
Ah, but it's not a completely new expression; it's a derivative work of the gnomes created by their parents, which is a derivative work of...
Contacting the all the original owners of the work (most of whom are not even human or alive) in order to purchase all the contributors' rights, would be extremely difficult. You can't just assume that you have inherited the rights from the dead ones either, since they have other descendants besides you. Orthodox evolutionary theory states that all life forms on Earth are descended from a single living organism (which is probably dead by now), so they all would have a claim to the inheritance.
Every living being on the planet is a part owner of every genome on the planet. That's about as close to public domain as you can get. So no, I'm not worried about anyone patenting or copyrighting my genome. Any living thing's genome is a derivative work of something that everyone owns the rights to.
---
As copyright owner of this comment, I authorize everyone to defeat any technological measure which limits access to it.
>5 other people have yet to be sequenced, not 4. I should know. I'm one of em.
(chuckle)
Bowie J. Poag
Project Founder, PROPAGANDA For Linux (http://metalab.unc.edu/propaganda)
Bowie J. Poag
The 500 MHz G4 is capable of sustaining One Billion Floating-point Operations per Second - one gigaflops. Its peak performance is claimed to be around 8 gigaflops. A "megaflop", it stands to reason, is either a venture which failed miserably, or just a guy with a big, limp penis.
The point is: if you're going to try to use facts to support half-baked analyses, at least get the facts straight.
To the editors: your English is as bad as your Perl. Please go back to grade school.
Yo Chris - thanks for the tag. I always feel that
the signal to noise discussions on slashdot
are pretty skewed. Who knows how this all going to
pan out.
I have to admit I think we have done pretty
well with the latest bioperl. Kudos for you
as well chris...
That's what Celera said this morning. No month but "by the end of this year."
I was at the hearing today at the House of Reps this morning on this topic and Dr. Venter of Calera said they use 64 bit alphas. No specifics though.
Ewan is heading up just such an open source project you mention. Check out www.ensembl.org.
In a more general way we are also working on tools over at bio.perl.org
Very Well written Sean !!!
See you in Helsingör
Copyright 1998 arne Verbatim copying and distribution is permited as long as this message is preserved
And on a slightly different note, if the offspring were a Boy, what are the chances that he will be a clone of you? :)
This space for rent. All reasonable inquiries will be entertained at proprietors discretion.
So, just how much patenting can Celera really do with this shotgun data? Especially if the public folks are looking at their half of the shotgun data, making inferences about function, and putting it in the public domain in parallel?
The big worry seems to be that they could be a tollkeeper for a large fraction of all genomic research via this patent route -- but its unclear from the press reports just how realistic this fear is ...
uh ... it's April 2000, aren't you supposed to be in a bomb shelter somewhere?
I recently was at a presentation by a human genome project researcher (doing C14 work) given to us geek types so we would better appreciate the gigabytes of info they're accumulating on the servers at alarming rates.
Anyhow, the scientist indicated that genome variation between individuals is something like 1 pair in 1000; e.g. down at the genomic level we really aren't that different.
But what a difference that 1 in 1000 makes on the final product!
Also, at least here (where I work), the genes are donated anonymously, so there's no way (yet) to attatch a particular sample to a particular person or ethnic group.
One one level, I figure its makes sense that a private company would be able to beat some government initiative, no matter how well staffed and funded.
On another level, I'm worried too, and I can see them trying to patent certain things because they got there first, rather than (I don't have a major problem with) them patenting their techniques for acquiring this intel.
Should there be a 'GPLing' of the genome? If so, just how could you?
-pbk
I get it.
Its one of those situations where waiting to start something can make the result come sooner. Of course, the success of the late starter (with the newer technology, like Celera) is predicated on the innovations of the first mover (like HGP.)
In this scenario, you can't have a Celera without an HGP.
Question: Are they working on these 5 people in parallel? Wouldn't that make sense?
-pbk
I think that the Human Genome is a prior work. If anyone holds a patent, it would be God, but she forgot to file it.
Will in Seattle
Well, they do!
FunOne
FunOne
Given the recent appeals court ruling on programming code, it only seems reasonable.
I know that Celera is patenting the genes it finds by the thousands, but won't I be able to use those genes as a way of expressing myself?
For example, I could use them to present a specific eye or hair-color, or a specific pattern of baldness. Would my rights to my own genetic code be protected now?
Work for Change & GET PAID!
Actually the first verse and chorus of Clone of My Own were originally written for FSF by Randall Garrett. Isaac Asimov, Robert Silverberg, and several others did contribute a number of verses; I don't thing RAH was one of these others, but I could be mistaken.
Rev Neh
... and there is no doubt, that one day he will be
where the eye of his telescope has already been
What if Newton had patented gravity?
Grades, Social Life, Sleep....Pick Two.
--Justin Mitchell
"2nd Place is a fancy word for losing" --Bender (Futurama)
I'm not a biologist, but aren't everybody genes different?
To insure that the map is correct wont they need to look at more that 4 other people?
The government classified anything that could perform a megaflop as a supercomputer. With the AltiVec engine, the G4 was capable of a megaflop, and thus classified a supercomputer. Apple just took advantage of an aging definition of what a supercomputer is and made the ads.
Pair up in threes. - Yogi Berra
The individual sperms do not have to contain different chromosomes. The differentiation occurs in the way in which the 23 chromosomes from the dad combine with the 23 chromosomes of the mom. The number of combinations, given the number of genes is horrendous which is why the chances of somebody giving birth to identical kids is negligible unless they are monozygotic twins. In which case they have the same genome. Farhat
At the intersection of computation and biology.
The fact that these two organizations are "neck and neck" should be a giant flag waved in the face of any patent examiners looking at gene patents. Part of getting a patent is that the new "invention" should be non-obvious to a practitioner knowledgeable in the field. It seems that what Celera is doing is rather obvious to a practitioner in the field, and there not patentable. Patents aren't a gold rush. It's not supposed to be about who gets there first; it's supposed to be about innovation. If I manage to count the five thousand fenceposts surrounding a farm, it doesn't mean that I should get a patent on fenceposts. Anybody can count fenceposts.
Heinlein remains one of the sickest bastards in american literature. -D
We're on the road to Tycho.
Craig Venter has promised this (on June 17, 1998 to the U.S. Congress):
[snip]Celera has never made a release of it's human sequence data, so they must have started their work less than three months ago. The media are obviously mistaken when they report that Celera started sequencing in September last year.
BTW the human genome project got a bit of support yesterday from the U.S. Senate,
So, say you could change something cosmetic about yourself genetically for a reasonable price. For example, what if a virus were available that triggered a whole-body genetic mutation, and the end result was a change in your genetic hair color?
Assuming you wanted that hair color, would you do it? Would the use of genetics for such things be unethical? How sacred is that individual genome that each one of us posseses?
What are the ethical uses of genetic information and modification? To cure disease? To select offspring attributes? There are LOTS of interesting questions that are going to be coming up in the next decade or two.
Get over it.
I'm a worried a WHOLE lot less that a private company has this than I would be if my Government had it!
No, you can't change it... but, males come equipped with one of each. Now, if they just took two of the X's, everything would be fine
-- Dr. Eldarion --
I'm thinking 100 percent... since you would be contributing your one of your own chromosomes to another one of your own chromosomes...
Well, that's an easy way to make clones of yourself, I suppose... just make one and the others will come *ahem* naturally.
Although, they would probably be a bit... uhm... screwed up.
-- Dr. Eldarion --
If I told you Gateway was a more efficient PC manufacturer than IBM because I took their total budgets and divided by the number of PCs they sell, you'd tell me I was being simplistic and stupid; IBM has a number of other corporate focuses.
The public genome project involves much more than raw human sequencing. It also funds technology development, physical mapping, genetic mapping, and model organism genome sequencing, amongst other things.
Likewise, Celera is being disingenuous in comparing budgets and timelines. In actuality, we are all using the same basic strategy and the same equipment, so the rate and cost determining factors are identical.
Celera intends to reduce their costs in two simple ways.
First, half their data will be taken from the public domain. Automated scripts from our friends at Celera download data nightly from our anonymous FTP server, a source of great continuing amusement to us, considering the corporate press releases that boldly say that "Celera has never relied on any public resources".
Second, they will not attempt to finish the genome to the high quality that we are aiming for, and it is that high-quality finishing stage that consumes expensive labor.
The combination of these might reduce their costs to about 0.10/base, so they could get away at $300M for the genome, compared to our $1000M. There is no way they can get under 1/10 of our costs; they've already spent ~$200 million or so just in one year of salaries and capital costs, and I have no idea what their supply costs are (but our *major* expense here is supply costs). Their slightly greater speed comes at a substantially greater incremental cost. Don't bullshit people about what a small efficient company they are: they are a big-ass biotech company with about a $6 billion dollar market cap.
And if their business model excites you, and convinces you that Celera is so cool, hey, here's some insider info: this November I plan to start Sean Genomics, Inc., and I will sequence the human genome in 1 day for $0, by downloading the data by FTP from WashU and Sanger, and I'll start issuing my own press releases about how I'm a zillion times more efficient that the Human Genome Project. Watch for my IPO!
Just another dead troll in a Baggie(tm).
"History doesn't repeat itself, but it does rhyme." Mark Twain
No - since we have 2 copies of each chromosone the child could get the a gene from fx the left of both parents. So the child would have a different chromosone pair as a result (actually the genes in the chromosones are mixed too IIRC) And having two identical copies of a gene causes many of the problems of inbreeding if I understand correctly...
Anyhoo. Just thought maybe people (particularly those ranting about us not having any info available to the public). Hopefully.
The streets shall flow with the blood of the Guberminky.
My Opinon. They are doing this in the stylish newly created 90's style hype/media driven fashion so many companies and the mass public now flock to......
What im saying is, if you are doing something so controversial as this you generally keep it a private thing until you have something, something more solid than these people do. They do not even have it all yet and they should have kept this all trade secret type stuff at any rate. *shrugs* They are going about this the *WRONG* way. nuff said.
Jeremy
I bet it was just a Mac G4..you remember those ads Apple was running about the US Government having classified the Mac G4 as a "supercomputer."
They are going to sequence the genomes of a total of five people. What five people? I'd interested in certain peculiar characteristics of these people. Things like colour, race, sexual orientation, hair and eye colour, heck maybe even what brand of beer they like.
The horrors of what the Nazis were trying to do during their disasterous 12 years in power should be a foremost in these researchers and, more importantly, their bosses minds.
Perhaps the little icon for this topic should be two a headed monster.
Actually, that'd be Isaac Asimov. He had a penchant for such funny little songs, something I can't recall RAH ever indulging in.
So, could they now patent that person's genome?
:) (I'm sorry, either you pay us royalties for each day you live, or kill yourself right now.)
If so, could they sue the person for patent infringement?
Or would the person have "first use" rights?
Yeah, I know, but it's fun to play...
BlackNova Traders
It's Shakespeare, you know ;)
--
It's a
-- Danny Vermin
Just to throw one more fact into the pile already posted by fellow scientists. I'm working in a lab where our main job is isolating and sequencing DNA, plants in our case. Its an extrememely tedious process. The point I wanted to mention was that there is such a thing as post-transcriptional modification with DNA. After the RNA has been transcribed sometimes an enzyme comes along and changes anywhere from a few to almost all of the bases in the strand. Not much is known how this works, but it is just one more thing that points just because you have the sequence it doesn't mean that it is all that useful. A majority of the DNA in higher mammals is repeats of things like ALU sequences which are leftover from things like retroviruses and have accumulated in the genome over generations. Why is it there? Well there really isn't a mechanism to remove it. There is going to be a really long scavenger hunt as they sort out the trash from the stuff that actually matters, and don't forget the introns/exons...but those aren't that difficult to separate. One of the more interesting albeit "noncritical" results of this will be the ability to make an accurate phylogenetic tree. It'll be very cool to be able to run Clustal W alignments of other species against the human genome.
Now the site will be jammed by the /. effect! all hopes of ever having the human genome made public are now vanished!
There are two kinds of people in the world: Those with good memory.
BTW, someone knows if it's Richard Stallmann genome? In case they found the gene responsible for GPL licensing and want to trash it!
Wouldn't You Go Blind If You Had Sex With Your Clone?
And When Does The Whole Gattaca Senario Set In? are Just How Useful Is One Person's Gene's? Does That Mean That They have 599,999,999,999 People Left?
`Lex - Find Me Here: Text Appeal
Unlike many reporters, Hemos was able to actually hold off on the hype and tell us that there are several more years to go in a short post. Thank you Hemos!
That's it. I'm no longer part of Team Sanity.
Correct me if I'm wrong:
1 base pair has 4 possible value: G, A, T, or C --> 2 bits/base pair
1 base has how many base pairs? I assume 1
3 billion bases per human. (Or 24 times 3 billion?)
Total data=3*2 billion bits = 6*10^9 bits = 75*10^7 bytes = 715.25 MByte
Looks like my sequence will not fit on a CD-ROM for backup. This might be a good reason to get a DVD RAM drive!
This is exactly what the more speculative end of the field addresses: Can (say) a virus be engineered to (reliably) make a single genetic alteration to a single spot on a specific chromosome in every cell in a patient's body? And if so, can something be done to trigger the expression of the new genetic state in that individual?
There are some ways in which it would not be impossible... skin and hair cells, white and red blood cells, sperm and ovum, for example, all replicate very frequently. Change the stock cells, and the next replication will do it. As a matter of fact, just about anything highly prone to cancer would be a potential target... which makes cancer a very good target.
Personally, I don't think any minor alterations to a virus are going to do it... they don't selectively modify chromosomes, they just invade, insert DNA/RNA, and trigger replication - with a less than desirable result, IE death of the cell. Viral tools can do crude DNA insertation, but not in a way that I would want to use in my own body.
Something more advanced, with pattern matching capacities, could be engineered into a simple psuedovirus structure... there have been chemicals engineered to photoactivate when they intersect some specific long sequence of DNA, though they are not replicative or durable. One of these coupled with a sophisticated insertation molecule might be able to do the mass corrections, though the toxin levels of the one that was engineered might have been prohibitive...
Whatever the form, nanotechnology is extremely young, and will require decades more to mature. Don't go expecting miracles in the next five years...
-- Still waiting for the Nike endorsement
The Human Genome Project is releasing "real" sequences into the public domain as they become available. Academics and private companies alike are using this information which will ultimately benefit everyone; the very nature of a public good. Celera is using the public database and their own work to complete the genome (read fix the holes in their own data and speed the process). Ultimately, they will market this dbase to biopharm/techs to speed drug development which will still require 10-20 years and mad development cash. The real payback goes to PE Biosystems. Celera demonstrates the process, while PEB will cleanup on sales of equipment (PEB has a majority stake in CRA). Unfortunately, a good source has stated that CRA intends to pursue sequence patterns. I had the "honor" of attending lunch with a CRA figurehead, Dr. "He's so boring I forgot his first name" Smith (Nobel laureate, JHU emeritus). After a seminar that resembled a shareholders meeting more than an academic gathering, he made it clear that they will seek patents on techniques and derived sequences. Although the genomic law environment is a tad murky; the patent office, President Clinton, PM Blair, and a recent EU court decision have "recently" consistently implied that broad patents will "probably" not be granted. PS Don't buy any of those stocks . . . especially on margin.
Ignorance . . . the ultimate American value.
The HGP will finish "draft" status by next june, my part will be at "draft" very very soon. we're spending tons of time now to figure out if we really are at draft status (3 fold coverage) which is something celera doesn't have to worry about, they can just crank up the pr machine in response to their stock dropping so abysmally without having to worry about peer review as they won't be releasing their data for quite some time.
they're also using specialized hardware from paracell I believe. the alpha es40s rock, compaq let me try one yesterday and it rocked, 3x speed of latest sun chips for blast and 4x for for threaded fasta searches.
mapping also now refers to positioning the segments of dna that were sequenced relative to one another.
to sequence something large like a chromosome you need to break it up into ~200kb fragments first in order to have a stable starting material. Next you have to break that 200kb fragment into 3kb and 10kb pieces at some fold coverage (determined by how accurate you wan't to be) which are what is actually sequenced
the mapping I do is utterly unrelated to genes and solely consists of figuring out how all those fragments originally fit together but it's still called mapping.
This is actually a really good question. I had always assumed that, as in the Human Genome Project, it was not one human being sequenced, but parts of the genomes of many humans. At least according to CNN however, it *is* a particular human being in Celera's case. One particular human being, whose entire genome is going to be sequenced. (In fact, the CNN article says this is only the first of six people.) If this report is really true (it is CNN after all) then I would be very interested to know who it was. I'm sure a lot of politics went into the decision...
I'm not going to pretend to be what I'm not: I am not affiliated to any gene mapping project, I am not a biologist (in any real sense of the word) and I have never knowingly participated in any cloning project/experiment. I hope this is apparent from the start of this post, right through to the end.
But let me say this, some of the follow-ups to the above message make statements about the impossibility of making a female clone from male cells. Let me say that that is wrong!
Okay, there are plenty of interpretations of what you want...what's a clone as opposed to a man-made combination of genes? I also admit male-to-female is the easier of the two(if your willing to accept the following to a degree), so that's why I can explain so simply here. Basically what makes a male cell male is a Y chromosome. Female cells simply can't have them(as a general rule). Thus whereas a Female cell will have two X chromosomes, a male cell will have an X and a Y chromosome.
By following text-book procedure, it would be technically possible to remove/disable the Y chromosome in a cell, then take the X chromosome from another cell(be from the original donor - ill advised - or a third party). The difficult part, and the part which I, of course, don't know anything about, is sticking the new X chromosome inside the cell nucleus and ensuring that the cells, with all its biased organelles and issues associated there-in, survive at however low a rate. This will produce a single, 'adult' cell. To extend the theme of a human clone, this would then lend itself to the 'Dolly the Sheep' model of producing a viable entity.
Now, by manipulation of the gametes, going for reproductive cells rather than 'adult' cells, other issues are raised, but a more straight-forward path seems open. The male and female gametes could then be merged in the traditional way and placed in a suitable 'surrogate', i.e. artifical insemination. This could be referred to as the 'trad-invetro method' (a particularly clever name).
The problem with changing a female cell to a male cell can be tackled on several levels, depending on your interpretation of 'clone'. Needless to say that without the introduction of third-party Y-chromosomes, the manipulation of genes in the nucleus becomes much more complex and, once again, something I'd have little idea about.
Now, once again, the 'simple' procedures above would require little-or-none of the high-tech gene-alchemy we expect because of sci-fi movies. But such alchemy would be necessary in the majority of cases to overcome genetic flaws...pretty damned tricky stuff that gene mapping goes a long-way towards aiding. Public Domain gene-mapping...maybe have the processes a company secret, but data shouldn't be restricted.
And that, my dear readers, is my post on the wonders of producing opposite sex clones.
Concrete analysis...
Obviously our environment has effects on who we will become, but consider identical twin (i.e. clone) studies:
When two identical twins are raised together, they usually develop completely opposite views, interests, philosophies, hobbies, etc. This is called "twinning" and it seems to be a basic human response to the need to be an individual.
However, some studies have been done on identical twins separated at birth - and they're amazing. One pair, for example, was reunited after forty-something years. They were both firefighters, they both had relatively the same income, they had both been married at roughly the same age, and their wives looked the same.
Remember - it might be in Michael Jordan's genetic coding to have the Drive (not just the ability) to play basketball - and unless some environmental situation "shuts him off", it doesn't seem unlikely that he, or any of his clones, would develop the same way.
"Beware he who would deny you access to information, for in his heart he deems himself your master."
As Sean Eddy noted, Celera has a way to go before delivering a finished human genome sequence. This only slightly diminishes Celera's ability to widely acquire utility patents on the use of individual genes for developing therapeutics and diagnostics (drugs and tests for diseases), and the small changes (mainly single nucleotide polymorphisms) that are believed to differentiate individuals' tendancies for disease or amenability to a particular diagnostic therapy. On Celera's so-called 'speedy' results, to my recollection the original public genome project was purposefully designed to take a more thorough and slow approach to getting a high-quality product at the end. Closing the gaps and finishing the hard-to-sequence parts was expected to be scientifically important in the long run, but unglamorous and less interesting in the medium term. So rather than go for just the exciting quick results approach, the public project decided to get all the genes and the intervening, non-coding, DNA, and the regions of unknown purpose, thereby spreading the finising grind and the exciting work among all contributors. Although incomplete, Celera's data--combined with the public data--is quite well enough to start mining off the low-hanging fruit and wholesale patenting the human genome with their 80%return/20%of-the-effort approach. Moreover, this will allow Celera & co. to refine their workflow and tweak algorithms so that while the academmics are grinding out the higher quality data, so Celera's analysis pipeline will be the worlds most highly-tuned high-dollar pipeline for analyzing that work for patentable content. A good team of biologists motivated with stock-options at Celera, trained and seasoned on the public algorithms for genomic analysis, would be very, very hard to beat. By rumor, Celera has far more computational resources than the public projects, and I understand that they have been hiring aggressivley in the math and computational sciences, as well as luring cash-poor graduate-student biologists to help pore over their data. Furthermore, Celera has wisely put the drosophila (fruit fly) genome data in the public domain so that it can be analyzed and the data from the fruit fly will be available to figure out what all the human genes do by comparison (homology mapping from a known example is the #1 way to find out what a gene does. Fruit flies are ~>90% similar to humans at the gene level). Hence they have the computational horsepower to rip through their data with any and all available algorithms, and they have or may soon acquire the biological expertise to refine their approaches for gene recognition to a patentable level. It is an unfortunate point that the public domain groups can't restrict the licensing of their software for use by Celera. The core of genomic analysis software, from raw-dna assembly to what-does-it-do gene analysis, has been almost exclusively developed by the academics. And the balance of good computational genomicists remains in the public domain. Remember that the human genome data isn't worth a cold cup of coffee without the computational algorithms. To quicly sift through billions of dna base-pairs you must get in the ballpark for what any-random-gene in all-that-data does--with the computational algorithms. Only then can you hire a biologist to close in with a tight patent on what that gene might be good for.But the discussions I've had indicate that the academics have never made a serious fight on the basis of use of their algorithms (or data) to reign in Celera or similarly operating high-throughput data- and legal-mining compaines. Still, there are a few of us, like Sean E., who are working to put a bit of the human genome's intellecual property in the public domain. But I think it would be fair to say there is a 10x imbalance of human resources and a 100x imbalance of funding between computational scientists dedicated to putting the genome in the public doman and scientists employed/dedicated to seeing Celera succeed. Most computational biologists I know are bystanding, not keen on patenting the genome, also not interested in a 'white knight' approach to take on a juggernaut opponent, and mostly trying to crank out better tools for genomic analysis for use by anyone who cites their work. So the public computational efforts are likely triage for a limited portion of the genome--at best--if Celera's patents hold up. As I understand it (I'm no lawyer) all the wall-street payoff, all the intellectual property, comes from figuring out what the genes & features in the DNA do so you can file a utility patent. This law is not well-settled, though I expect Celera is working hard to couch their position in the single-gene-patent precedents which allow companies like Genentech (Human Growth Hormone, 15-20 yrs ago) and Geron (telomerase-like genes believed to control aging, mid-late 1990s). Celera's patents could be overruled or blocked by statute if it is deemed not in the public good. That may not be to the liking of large pharmaceutical companies who can out-bid others for the rights to the choice genes, though, so it would take a *lot* of political pressure to keep Celera from having rights to the human genome this way. In the days of dot.com dollars, Celera is huge to the scientists but tiny compared to the quiet interests (top 20 pharmaceutical firms) who would get a competitive advantage by keeping Celera's patent stable on retainer if they succeed. Still, you could email your congresspeople if this issue is important to you. Or maybe you can spare an aging $150K smith-waterman accelerator, 2.5 terrabyte RAID, and some high-wattage Oracle8i licenses? -RPO endnote: I hope Sean E. and others will correct any inaccuracies from my few thoughts in this tiny comment box.
RPO
What you are reffering to is annotation of the geneome, which basically marks the genome for restriction sites, and lots of other hideously complex genomic information. Drosophila Thanks. Andrew Hutchins
The way to succeed in biological sciences is to study what the media is interested in and not necessarily what's practical. Gene sequencing today has the media attention yet the foundation of gene sequencing, bioinformatics and protein modeling is impossible to get grants in. Since the DNA sequence is useless unless you can process the data we see how important media coverage is in the world of biology even though none of the data can be used for anything.
Inbreeding is only an issue if there are bad recessive genes. Heinlein himself addressed this at the end of _Time Enough for Love_, where Lazarus Long was finally jumped by his twin female clones.
:}
/||\
Now THAT is what i call a rich fantasy life.
__
(oO)
Hand me that airplane glue and I'll tell you another story.
According to this week's Time Magazine, the Human Genome Project is now estimating that they will finish in November of this year, unless I grossly misunderstood the article.
> Wake up and smell the coffee.
I think your tin foil cap is slipping. Better adjust it - FEMA is trying to take control of your mind so that they can use your genes to create a race of superhuman zombie soldiers.
It seems unlikely, but it isn't.
I forget what 8 was for.
This is what the outcry is over. It's also why their (and many other 'biotech' firms') stock evaluation is soaring through the roof.
After the HGP had ran for a few years a group splintered off to pursue it purely for profit. That's Celera. They've promised to allow access to the information for researchers, but have never deatiled to what extent. They obviously aren't going to allow outside research to be done with any genes they claim a patent to, and that's been the sticking point in most of the past cooperation talks.
Also remember that the announcement made by Clinton & Blair a few months ago gauranteeing the freedom of the genome only applied to the HGP. They would have had to have completed the first map in order for it to mean anything. Celera's rather amazing accomplishment now will mean a real big headache for everyone who's not one of their investors.
A possible scenario is that you fully develop a way to clone yourself, but can't because certain genes giving you immunity to some diseases are protected by a patent. It's really horrifying. Medicine is about to get as nasty as computer software. Everyone is going to sue everyone over everything, all trying to get any slight advantage they can. And people will be dying so stock prices can raise a few tenths of a point...
The most interesting article in the March 24, 2000 Science issue that described the recent
fly sequencing is comparative protein complexity.
Once you have the genome, you can start deducing better the mix of proteins in organisms. Proteins do most of work of life and are harder to analyze than DNA. Only a few percent in humans are understood.
These three organisms: worm, fly and yeast
were the first three complex organisms to be
fully sequenced. (Mouse, human, dog, corn, rice, and tobacco are in the works.)
It turns out that the worm is slightly more complex
than the fly, and both are about twice as complex
as yeast. It is expected humans will come in
about twice as complex as a worm. We'll know in
a few months.
Protein complexity is not necessarily the same
thing as organism complexity.
All organisms on earth have been evolving for
four billion years, so have the same chance
at complexity.
Genetic mechanisms for managing complexity have
been evolving too.
It may be humbling to find that from a genetic
measure, humans are simpler than some other
plants and animals.
__________
If you can go to bed, knowing you did a valuable thing today, you're very lucky. If you can't... it's not bedtime
Check out this Globe and Mail story about Sick Childrens Hospital in Toronto sorting the map - with a supercomputer. I've seen pictures - SGI Origins all over the place. Cool hardware - now let's hope they "Do no harm" with any knowlege they gain.
"Depression is merely anger without enthusiasm." - Anonymous
I did hear at one point that they were going to gang together 400 or so 4processor AlphaServer ES40's specifically to handle either the assembly or analysis portion. The 400 servers X 4 600mhz EV6 Alpha chips would give you 1200+ cpu's in the cluster...the final version of this system is what they claim will be the 2nd fastest civillian owned supercomputer on earth.
I don't work for Celera so mistakes made above are my own. I'm just a bioinformatics hardware geek and a big supporter of Alpha-for-life-science-research type projects. From a infrastructure geek's perspective what Celera is doing is just amazing...
10 years ago the state of the art was pretty poor. The HGP estimates were based on that technology.
Celera's relationship with PE allowed them to get their hands on tons of the new 6700 series DNA sequencers. Without them Celera's effort would have been impossible.
So-- Ventor does deserve some credit -- he was smart enough to realize that the revolution in sequencing (plus a cozy relationship with PE) had changed things enough to make a a large-scale private effort possible.
just my $.02
Lets say Celera does finish the mapping before the Genome project can. Celera then sells to researches data from the mapping. What happens when the Genome project completes and gives the information away? Can Celera call it theft of intelectual property?
I found this article on the cataloguing of the Genome Database in the Globe and Mail. It talks about the why and how of the database. Here's a quote: In the one year since Canada took possession of the Genome Data Base -- which shares a small room with a large air conditioner -- the on-line system has logged 20 million hits. Estimates suggest it serves more than 1,000 scientists in 50 countries.
IMHO, as per,
J:)
Oh well, no point in steering now.
... what's the "largest private supercomputer" Celera claims to have used? (quote is from the Wired article). Anybody got any info?
engineers never lie; we just approximate the truth.
Since they're the first to do it, how can anyone be sure of the veracity of their claims?
>
Should I RTFM? IS there a FAQ on this somewhere?
-pbk
Well, now they think they can produce a carbon copy of a human being at will -- or worse yet, a modified copy which has exactly the characteristics they want: Obedience to secular authorities, low IQ, lack of imagination, lack of faith, etc.
This Black Helicopter moment has been brought to you by Genetic Engineering. At GE, we bring good things To Life.
But somewhere out there there's a person who's about to become the benchmark human that we're all going to be measured against .....
This brings up the whole issue of patenting and the Intellectual property ownership of part/all of the human genome. It is my understanding that parts of the human genome have been patented already, does this mean we no longer own ourselves?
If I were to be marry and have a child would I be violating their patent by using the patented parts of the human genome? Ok so you could argue that a natural process can't be patented and the patents are for secondary uses, but what about medical cloning. If experiments continue into therapeutic cloning for the production of stem cells and potentially organs would this non-natural process not be a patent violation.
If by chance God does turn up for his thousand-year reign could he not claim some kind of prior art? Ok so that's probably not an issue the patent courts are going to have to deal with in the near future but the fact that patents can be granted on existing genetic material does raise some interesting questions, by granting patent in this manner the patent office is dismissing the idea that the genetic makeup of us/animals/plants may have been designed and is thereby encroaching on an area of belief held dear to a lot of people.
Basically they are betting that at least some scientists will pay for their map because of the way in which it rendered, maybe it will be easier to use, look prettier, run sequence search algorhythms faster, or something similar. But two independent copies of the genomic map (done in two scientifically proven methods) can only be better than one, so many scientists will probably end up using both maps for some percentage of their work/research/experimentation.
You will just have to pay for the bells and whistles (and speed of release) of Celera's map.
On a bit of a serious note, if that sex led to actual childbearing, wouldn't there me a MASSIVE inbreeding effect?
I mean, if having children with family whose genes are merely close to yours produces it, then what would happen if one was to have a child with someone that had the EXACT SAME genes as themselves, only a different sex?
-- Dr. Eldarion --
Celera mapped the genetic structure of the fruit fly recently. They claim that they will have the sequenced genes of their human subject assembled in three to four weeks in an article at CNN
I stole this sig from a more creative user.
Last time I checked the human 'rough draft' from the public project had about 80% of the sequence complete in draft form and in the public domain. The Celera project has nothing in the public domain except a few press releases.
I update my databases every night from the HGP. It is doubling in data volume approximately every 7 months and the doubling time is getting shorter.
Moores law eat your heart out.
The HGP is providing us with data faster than we can analyse it, and really opening up a whole new level of understanding of how things work. One of my colleagues complained to me after I had given a seminar on Genome analysis that his labs old laboroius techniques of analysing family pedigrees and careful selection of regions to look for genes was being blown apart by the public sequencing projects.
We are entering a new era of biology, one in which a biologist will need to be as handy with a keyboard as with a pipette. If you want to be a successful molecular biologist you will either need to be very, very good or have good data analysis skills.
Enough of a winge. Any open source programmers out there fancy getting involved in writing code to help with the human genome analysis? plenty of odd tasks to go round.
Dr. David Martin European Molecular Biology Network node manager.
--- Four bases should be enough for any genetic code
Celera is actually doing two things here:
1. Getting the raw sequence of the human genome and marking off all the genes we already know, as well as some "best guess" genes that are similar to other organisms that have been sequenced. This will be available from them for free to everyone.
2. They then plan to go after genes we don't really know. A little explanation:
Genes are how the body stores the information to make proteins (which get made into enzymes, cell signalling molecules, whatever...). They also make other things, but I don't want to complicate this. Largely, it's proteins that scientists are interested in becuase they are the machinery through which the body works. Cancer, for example, is caused largely by proteins that misbehave and refuse to do their jobs.
Just knowing the sequence of the human genome tells you little about the functions of the genes. The proteins made from those genes must be studied and characterized. This is where Celera's business model kicks in. They plan to identify and characterize as many proteins as possible. This is a non-trivial task, given that some molecular biologists spend their entire lives working on one protein. Celera plans to look at the protein-protein interactions as well as their locations within the cell to get an overview of what all the genes in the human body are actually doing. It's real "big picure" stuff", meant to serve as a starting point for future research. It is likely that many of these proteins will have value as targets for drugs, and I think Celera plans to patent these genes to make money. They will at the very least charge a subscription fee to look at all the protein data they have collected. I am fairly certain that other companies have already patented human genes...without the patents, there is not a whole lot to protect a drug from being stolen by competitors.
All of Celeras research will be at an ENORMOUS cost to the company. Should they make all the info free? The bottom line is that realistically, you and I are not going to develop the cure from cancer because we ran a perl script on the human genome. It takes a Pharmaceutical company with deep pockets to pay for all the FDA trials and get the drug ready for "prime time". Celera knows this, and they know these companys will shell out wads of cash to get info about as many proteins as possible. It is possible that university researchers will not have the money to pay for this information. But there is so much research to be done, the big pharmas will likely fund projects at universities to look into some of these genes more closey, so many of them will get what they want anyway.
http://www.pecorporation.com/press/prccorp011000.h tml
[excerpt] "Celera's mission is to become the definitive source of genomic and related agricultural and medical information. Celera's information will be available on a subscription basis to academic and commercial institutions who will have access to tools for viewing, browsing, analyzing, and integrating data in a way that will assist scientists in accelerating their understanding of the human genetic code."
And then there's the courts and governmetns. Both the UK and the US govs. had indicated that they might not be too happy about a company attempting to patent the human genome. It certainly isn't too clear what it means to patent a gene sequence, that simplier issue is yet to be sorted out.
It should be remembered, however, that genes are not an exact blueprint that we will follow. They allow for an expression of a trait. They do not guarantee that it will be expressed. Your dad could be Michael Jordan, but if all you do is sit at your computer and eat junk food you won't make the NBA. To often, it seems that genes are portrayed as concrete instructions on who we will be. Sometimes leading them to be used as excuses for personality/traits. It is the classic nature/nurture debate I suppose. It is just worth remembering though, that although not totally irrelevant, genes are not the sole determinant of one's self. I am in no way doubting the significance of this medically in curing certain genetic diseases, but I am weary of the way I see genes being portrayed by the general public in terms of their effect on who we are as people. ---Lane
What's the point of moderating?!
I'm curious: how well does gene sequence information compress? Is this effectively random data, or are there patterns?
I can see the disclaimers now:
The GeneStor PeopleBackup(tm) device can now store the complete* contents of your genetic makeup!!
(* Storage assumes 2x data compression. Results may vary.)
At least someone now has the technology to do offsite-backups of people... granted, there'll be a certain amount of data loss since the backup fileset was created (birth), but now, at least, there is the beginnings of real disaster recovery technology.
Imagine: Our friends at Legato could license Celera's technology and produce "WetWorker" -- with the ability to put your genetic data on CD-Rom for easy transport to offsite storage. Then, when your friendly, egocentric ocean liner captain decides to go "All Ahead Full" on a foggy night in the North Atlantic AFTER receiving an iceberg warning, you can rest confident that your family can always recover you from archival backup.
I'm aware that there are shortcomings (especially the part about "loss of all data accumulated since birth"), but after all, the centerpiece of any backup software isn't ease of recovery, it's ease of deployment. The data can always be reconstructed from "incrementals" (it pays to take good notes...).
This is my opinion and my opinion only. Incidentally, IANAL.
MOO;IANAL.
There used to be a picture linked here.
I don't think you could just "change" a Y chromosome to an X chromosome. I believe they're entirely different. Think about it, Y chromosomes give you the ability to drive well, while X chromosomes just give you the sense not to wear the same socks two days in a row.
-B
-rpl
Literacy is in short supply amongs most around here.
Q.E.D.
The human gene sequence is in the public domain and will remain there - anything else would be ludicrous (although I agree that when it comes to the law ludicrous seems to be perfectly acceptable. Witness patenting software algorithms). What I believe they will get the patent on is their process for deriving the gene sequences - which is perfectly acceptable. They will also have the rights to their database of human gene information, which they can license the access rights to. The Human Genome Project will be making its results publically available, so it might become a matter of whose database provides the most ancilliary information.
"The first time I got drunk, I got married. The second time I bought a chimpanzee, after that I stayed sober" Arian Seid
Unfortunately, the whole gene patent scandal is because of this point exactly... they *are* being awarded exclusive rights because they got there first. Bad, bad, bad, bad, bad.
I have every right to do whatever I want with any gene I've sequenced myself, damnit! I shouldn't have to pay royalties to someone because they sequenced it first!
The analogy is the spanish and portuguese "claims" to the americas, not a translation of Vergil.
-- Still waiting for the Nike endorsement
Great, now how much longer until a public beta release?
------------
a funny comment: 1 karma
an insightful comment: 1 karma
a good old-fashioned flame: priceless
this sig limit is too small to put anything good h
Is anyone else bothered by the fact that the first group to have a complete sequencing of the human genome is a private company? If anything ought to be in the public domain, all other arguments about software, music, etc... aside, it is the human genome. After all, everybody already has their very own. Celera deserves to reap the benefits of getting there first, but only until somebody else can get there as well. If another group finishes the sequencing, they have just as much right to use it as Celera. It's not like Celera has created an original work-- they've just finished reading through the genome first.
I really hope that the HGP places this information in the public domain as soon as possible, and refrains from signing any exclusionary deals with Celera that would prevent this information from being free.
www.eFax.com are spammers
Oh give me a clone
/||\
Of my own flesh and bone
With her Y chromosome changed to X
And when she is grown
My very own clone
She will be of the opposite sex (hurray!)
Clone, clone of my own
With her Y chromosome changed to X
And when she is grown
Since her mind is my own
She'll be thinking of nothing but sex!
(written by Robert A Heinlein)
__
(oO)
Hand me that airplane glue and I'll tell you another story.
SEQUENCING means creating a complete list of the nucleotides in order. If you had this information, you could actually synthesize the entire genome of the individual. [There are some sophisticated niceties like methylation that distinguish the synthesized version from one extracted from a human, but it's essentially complete.] There are other factors (like which regulatory binding sites are actually bound, by what proteins; exact state of histone supercoiling, etc.) that control gene expression enough to keep this from being a working human genome, but it's awfully close.
MAPPING means determining distances between known genes. Using this information, you can deduce where the various genes are, the approximate location of specific unknown genes, and many other useful facts. A detailed map is a good starting place for hunting down a gene, so you can locate and sequence it; it also can tell you what traits are likely to be inherited together, etc.
A "sequence" is a complete blueprint (though there are details that aren't covered by sequence alone) A map is like a geographical map that shows where all the cities and large towns are. There are still many factories, facilities, and industrial complexes off that map -- not to mention all the roads, rivers, mountains and utility lines. ETC.
A sequence is a lot more information, and a wonderfully compact database - at 2 bits per base pair (4 possible cases), you could fit a complete human genome in under a gigabyte. (That's only one human, however.)
Naturally, even once we had the genome (or preferably a few thousand individuals, to let us get a real handle on variations), we could still spend decades or centuries figuring out what it all meant. 3x10^9 bases is a lot of info. You thought it was hard trying to trace western civilization in the first million digits of pi.
I am not a Molecular Biologist - anymore. But I was, about 10 years ago.
__________
If you can go to bed, knowing you did a valuable thing today, you're very lucky. If you can't... it's not bedtime
Any reasonable person would define "complete" as this: there's three billion bases of human DNA in 24 different linear chromosomes. The sequence is complete when you can give me a DVD with 24 files on it, each of which contains a contiguous sequence of a human chromosome.
That may never happen for any large animal or plant genome. Too many regions of a genome sequence are an ungodly mess, repetitive and difficult to sequence.
The public worm (C. elegans) project, at 98 million bases, defined "essentially complete" as "we've come as close as we can to complete using existing technology". We have 97 million bases sequenced and about ~50-100 remaining gaps.
The fly (Drosophila melanogaster) project, at 180 million bases in size, was recently declared "substantially complete" by Celera. They have 120 million bases of sequence, with several thousand gaps. The fly has more extensive regions of repetitive sequence than the worm.
The human, at 3 billion bases in size, is nowhere near complete, either by the public (us) or by Celera, no matter what Celera press releases say.
You need the following steps to get close:
1. shotgun coverage. Technology limits us to reading ~500 bases of sequence at a time, so we have to blow the genome to bits, sequence millions of fragments, then assemble it all back (computationally) into a contiguous sequence. Because a successful assembly relies on deeply redundant overlap amongst the fragments, we need ~8-10x shotgun coverage (24 to 30 billion bases) to try to assemble the human genome. The fly genome was shotgunned to 12x coverage to achieve the results Celera reports.
2. Assembly. Once you've got shotgun data, you can try to assemble the genome from those fragments.
3. Finishing. The automated assembly (like the fly genome now) will have a great number of gaps. These must now be closed, more manually, by expert molecular biologists; the gaps represent regions that are biologically difficult to sequence.
The actual science behind the Celera press release is that they have partially completed phase 1. They currently have 4-5x shotgun coverage of the human genome, about half of what they need for a proper assembly. They intend to get the other 4-5x coverage from the public "rough draft", which is at about the same stage Celera's project is in.
The two projects (Celera and public) are neck and neck in this "race". The difference is that we acknowledge that our sequence is a rough draft at this stage; whereas Celera claims that their sequence is complete. Celera has every right to spin their project to their investors any way they feel is appropriate, but scientifically, they are being rather disingenuous if not dishonest.
conflicting oblig. disclaimers: I'm a co-PI on the public project, and I (accidentally, through an acquisition) also hold substantial stock in CRA.