|Feature Article - October 2015|
|by Do-While Jones|
The Human Genome Project taught us as much about politics, power, and geneticists, as it did about human genetics.
In the weeks leading up to the publication of last month’s newsletter dedicated to The Failure of Genetics, I read, in chronological order, every article about the Human Genome Project published in the professional journals Science and Nature. It was like reading a murder mystery for the second time, knowing from the first page whodunit. I saw clues I didn’t see when I read those articles the first time a dozen years ago.
This review of the history of the Human Genome Project gives us a peek behind the curtain, showing how science really works. It provides a concrete example of how political and financial forces shape scientific research. It answers the questions, “If science is against the theory of evolution, why do so many academics defend it?” and “Is there really a conspiracy to teach a false theory?” But let’s save those questions for later.
The Human Genome Project was controversial, but not for the reasons you might expect.
Of course, there were people who objected on religious grounds, saying that the structure of DNA is a secret only God should know, and could lead to terrible consequences if the information fell into the wrong hands. Since the professional journals tend not to be too concerned about religion, they didn’t address that issue—and neither will we. So few people seriously considered the moral implications in the professional scientific literature that it didn’t really rise to the level of controversy there.
The first controversy in the scientific literature was the controversy over whether it would be possible to fully decode the human genome.
The "job" is to map the chromosomes within 5 years and to decipher the full nucleotide sequence, all 3 billion base pairs, within 15 years-and at a total cost of no more than $3 billion. "If we go along the way NIH usually does, it could easily take 100 years to get the sequence," said Watson, who outlined NIH's plans in San Diego last week at the Human Genome 1 meeting sponsored by Science. 1
In 1989, Watson thought it was unrealistic to get the job done by 2004, and thought it might take until 2089 to do it. In fact, the job was essentially finished in 2001 for far less money. We know that now—but he didn’t at the time. So his concern was valid, and the controversy over whether it was technically possible was legitimate.
But there was another controversy centered around something called “Big Science” in the professional literature (although the following quote doesn’t happen to use that term).
Nevertheless, it has been the idea of obtaining a complete readout of the sequence-all 3 billion bases of it-that unquestionably fueled the excitement. The gargantuan scale and cost of such an operation, which might consume 30,000 man-years of effort and $3 billion only seemed to make the prospect yet more exciting. …
James Watson told the NIH gathering that although he had qualified support for the proposal, "everyone else at Cold Spring Harbor was against it." These people are young, he explained. "They are scared that if sequencing goes ahead there will be fewer funds available for their research." With a megaproject sucking up $3 billion, there is a real and valid fear that funds will be diverted from existing research. 2
In 1986, young geneticists realized that only the most experienced scientists were likely to be assigned to the project, so they might lose their funding. Scientists working in fields other than genetics feared that research funding for other subjects might be reprogrammed to support the Human Genome Project.
A dearly departed friend of mine, James L. Rieger, once told me the difference between a scientist and an engineer. I never forgot it.
When a scientist makes a great discovery, the first thing he thinks is, “Where can I publish it?”
When an engineer makes a great discovery, the first thing he thinks is, “How can I make a buck with it?”
It is generally believed that engineers are motivated by greed—but scientists are noble individuals motivated by the search for truth. That may have been true in 19th century Europe, when science was the hobby of wealthy men who financed their own research, and gathered in snobbish royal societies to discuss their discoveries. Those days of self-supporting science are gone. Today’s science is financed by huge government grants, and there is cutthroat competition to get those grants.
We now know it did not take the feared 100 years to decode the human genome. In fact, it didn’t even take the estimated 15 years. The job was done three years early, and under budget because private industry brought competition into play. Here is how it happened.
The recent announcement by Perkin-Elmer of a new, fully automated sequencer (ABI PRISM 3700) permits a reevaluation of strategies for completing the human genome sequence. This instrument is a capillary-based sequencer that can process about 1000 samples per day with minimal hands-on operator time (about 15 min compared with about 8 hours for the same number of samples on ABI PRISM 377s). This reduction in operating labor, coupled with automation of sample purification and sequencing chemistry enabled by the sequencer's improved detection sensitivity, suggests that the tens of millions of sequencing reactions necessary to complete the human genome can be performed more quickly and at lower cost than previously anticipated. The Institute for Genomic Research (TIGR) and Perkin-Elmer have started a program to complete this task within 3 years using this new technology and a whole-genome shotgun strategy that obviates the need for a sequence-ready map before sequencing. We intend to form a new company to carry out this venture and develop a commercial business based on these efforts. The cost of the project is estimated to be between $200 million and $250 million, including the complete computational and laboratory infrastructure to develop the finished sequence and informatics tools to support access to it. 3
In fact, they did form this new company, and it sparked even more competition.
Many scientists were skeptical last May  when DNA sequencer J. Craig Venter and his private backer—the Perkin-Elmer Corp. of Norwalk, Connecticut—said they were going to decode the entire human genome in just 3 years. At the time, the government-funded Human Genome Project wasn't due to deliver the goods until 2005. To some academics and government genome sequencers, Venter's pace seemed too fast to be credible. Then, in August, Incyte Pharmaceuticals Inc. of Palo Alto, California, joined the race. It said it was going after the entire human genome too, aiming to get just the genes in 2 years. Now, faced with growing private competition, the skeptics of rapid sequencing have become believers. In a radical change of plan, the chiefs of the U.S. genome project announced this week that they intend to match the private sector's pace and deliver comparable results just as fast.
The U.S. National Human Genome Research Institute (NHGRI) unveiled a 5-year plan this week that promises to produce a “working draft” of the human genome—including highly accurate sequences of most of the protein-coding regions—by 2001. The plan also promises to yield a polished, gold-standard version of the entire genome by 2003, 2 years ahead of the old schedule. If successful, this scheme will not only speed up the pace at government-funded labs but also, according to some of NHGRI's advisers, release data so rapidly that companies such as Perkin-Elmer and Incyte may not be able to get exclusive rights to all the DNA they hoped to patent. 4
Two private (profit-motivated) companies competed to get the job done, and the government tried to keep them from making a profit doing it. How noble of the government!
Eventually, the race ended in a tie, sort of.
Beaming at each other, longtime rivals Francis Collins and J. Craig Venter shook hands in the East Room of the White House on 26 June  as they declared joint victory—and announced an implicit truce—in their race to decipher the “book of life.” … What's more, the two former adversaries, who until recently have minced no words disparaging the other's work, said they hope to publish their work simultaneously in a peer-reviewed journal sometime this fall (see p. 2294).
This very public and very carefully orchestrated denouement—which required diplomatic skills akin to those behind the Camp David Peace Accord—brings to an end one of the most high-profile fights in recent biology, one that pitted a publicly funded consortium of scientists, led by Collins, against Venter's upstart company, Celera Genomics of Rockville, Maryland. With obvious relief, Collins and Venter agreed to forgo the barbs and share the credit for a biological tour de force that many scientists thought was impossible a mere 15 years ago. 5
This scientific advancement was made possible because private industry realized one way money could be made is by selling patented machines that decode DNA. Since then, many scientists have bought these machines and used them to decode the DNA of other living things. New genomes are published in the professional literature every few weeks now.
The other financial motive was the possibility of patenting some parts of the human genome. That might shock, scare, and confuse you.
Don’t worry. You won’t be tested to see if your DNA contains a patented sequence, and have to pay royalties just to stay alive. They aren’t going to insert patented DNA sequences into embryos to make super babies to sell on the open market.
There is an ethical and reasonable way to make money from patented DNA. One can not only patent a thing—one can also patent a process to make things.
Living things have natural defenses against disease. Their DNA manufactures chemical substances which fight infections. If one knows what DNA sequence produces the natural antibiotic against a particular disease, one can use that DNA in a laboratory to make that antibiotic, and convert it to a pill or liquid which can be sold for a profit. The profitable process of using a particular DNA sequence to produce a particular medicine can be patented (unless the government chooses not to grant the patent).
In the past, biotech company scientists looking to develop new therapies for human diseases had to start with a protein already known to be a key player in the disorder, insulin in diabetes, say, or human growth factor in dwarfism. They would then clone the corresponding gene, and with it manufacture the protein to use in therapy. Now, HGS and other companies are mining large databases of human gene sequences, looking for previously unknown proteins that might have therapeutic value. Once promising genes are identified—often by their structural similarity to known molecules—company scientists screen the genes' protein products in cells and animals for medically useful effects. 6
So this is really no different from the standard pharmaceutical practice of analyzing the chemicals in traditional herbal remedies and synthesizing the same chemicals to put into pills. The process of using DNA sequences to produce the needed proteins is patentable.
With this background, we can finally answer the questions we posed at the beginning of this essay. “If science is against the theory of evolution, why do so many academics defend it”? and “Is there really a conspiracy to teach a false theory?”
The answer to both questions is, “Big Science.” There’s no Vast Left Wing Conspiracy coordinated by some shadowy figure, telling all the professors what to say. College professors are smart enough to know that they need funding, and need to be in the club to be respected and successful, and independently know what they need to teach to get that funding and stay in the club. It’s not a conspiracy—it’s just economics. Scientists have to get paid, and have to pay for their expensive equipment. To do that, you either have to produce a product or sell a story.
Paleontology isn’t rocket science. In rocket science, sooner or later, you have to actually build the rocket. An eloquent presentation about how the rocket will work might convince sponsors to finance the project regardless of whether or not the theory is correct; but laws of nature aren’t swayed by a silver tongue. If the theory is wrong, the rocket won’t fly, no matter how convincing the argument, or how prestigious the alma mater of the presenter.
Paleontology can’t be put to the test. A fossil tooth may look like the teeth of other creatures; but that doesn’t really prove anything. A believable story isn’t necessarily true.
Paleontologists don’t produce a product, so they have to produce a story. New versions of the theory of evolution are produced all the time because nobody pays for the same story a second time. This month’s Evolution in the News column is a perfect example.
Yes, there is a religious component to the Theory of Evolution, too, which is well recognized. The Theory of Evolution is the creation myth of atheism. That can be a motivating factor for a particular scientist.
But if you are the head of a research department of a large university, the responsibility of paying the salaries of everyone in your department is a more compelling motivator. You need to come up with a story about a new possible human ancestor, or life on Mars, to get funding for your research. Furthermore, you need to protect your turf, as this month’s Evolution in the News column shows as well. You need to be the acknowledged leader in the field so that you get the grant—not your competitor.
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of the Month
L Roberts, Science, 13 October 1989, “Plan for genome centers sparks a controversy”, pages 204-205, https://www.science.org/doi/10.1126/science.2799383
2 R Lewin, Science, 8 August 1986, “Shifting sentiments over sequencing the human genome”, pages 620-621, https://www.science.org/doi/10.1126/science.3726552
3 J. Craig Venter, et al., Science, 5 June 1998, “Shotgun Sequencing of the Human Genome”, pp. 1540-1542, https://www.science.org/doi/10.1126/science.280.5369.1540
4 Eliot Marshall, Science, 18 September 1998, “NIH to Produce a 'Working Draft' of the Genome by 2001”,pp. 1774-1775, https://www.science.org/doi/10.1126/science.281.5384.1774
5 Elizabeth Pennisi, Science, 30 June 2000, “Finally, the Book of Life and Instructions for Navigating It”, pp. 2304-2307, https://www.science.org/doi/10.1126/science.288.5475.2304
6 Ingrid Wickelgren, Science, 13 August 1999, “Mining the Genome for Drugs”, pp. 998-1001, https://www.science.org/doi/10.1126/science.285.5430.998