Synthetic Biology

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by Bill Sardi by Bill Sardi

In the Brave New World of uncharted biology, does everything go? Where will biologists stop in their directionless frenzy to acquire basic scientific knowledge?

The latest fad among biologists is called synthetic biology. The small group that calls themselves synthetic biologists are already squirming at the thought of regulation, fearing limits will hinder their efforts to reach as yet undefined goals. The whole idea of synthetic biology is to improve upon nature, but there is a lot of gibberish coming from the mouths of these biologists that makes the most avid science buff begin to question what is going on.

Synthetic biologists claim they intend to create bioengineered organisms that can “produce pharmaceuticals, detect toxic chemicals, break down pollutants, repair defective genes, destroy cancer cells.” [The New Atlantis, Spring, 2006] These are laudable objectives. But there is a dark side to the direction they are taking.

It’s not that humans don’t already modify nature and transform biological systems. The cross-breeding of watermelons to produce seedless varieties, or grafting varieties of flowers to create, for example, new colors of roses, has already been accomplished without hesitance or harm. Gregor Mendel’s work (1823—84 AD), which began by crossing varieties of pea sprouts, continues today. But it has gone beyond that.

Beyond GMO

Synthetic biologists extend their work even beyond the concerns of genetically modified (GMO) foods. They want to design new strands of DNA into sequences that result in totally man-made viruses, no part being derived from DNA sequences found in nature.

Keep in mind, even with regulations in place, GMO “Franken” foods have crept into the food chain. Even with regulations in place, bees cross-pollinate GMO crops with natural varieties. GMO foods have been developed with a good intent, to develop crops that resist insect attack, but may result in upsetting the food chain. British researchers recently counted fewer bees and butterflies in GMO crops. [Proceedings Biology Science 2005 Mar 7; 272(1562): 463—74] Despite public objection, GMO soy and corn have been consumed by humans without proper labeling and notification. Will newly designed biological systems made by synthetic biologists secretly be released for use, as has GMO? Viruses can be used as vectors (vehicles) to secretly vaccinate human populations.

What synthetic biologists propose is more outrageous and dangerous than GMO crops, and it is easier for them to skirt around any rules and regulations. Synthetic biologists work inside hidden laboratories, not in open-air crop fields. They can place an order to build whole new viruses from synthetic DNA by simply ordering viral DNA from a genetic synthesis company. [Nature May 25, 2006]

Synthetic biologists are comprised of a group numbering no more than about 500 at present. They want to use bits of DNA, called “bio-bricks,” to build pseudo-organisms that can grow and act (even replicate) in more precisely controlled ways — creating “machines” which are “not quite like anything found in nature,” explains Alex Steffen in an online scientific blog [May 5, 2004].

Oh, Synthetic biologists aren’t going to create the blob — well, not just yet anyway. They claim they are going to police themselves, mostly limiting their activity to changing short chains of DNA in viruses, which are parts of DNA that can only replicate within living host cells. But synthetic biologists may have other agendas. They refer to “redesigning life” to “generate chemical systems that support Darwinian evolution.” Albeit, they reveal they intend to create “the bridge between non-life and life,” according to two chemists from the University of Florida who count themselves among the ranks of Synthetic biologists. [Nature Reviews Genetics, July 2005]

What do synthetic biologists want to prove?

Just exactly what do the two aforementioned chemists at the University of Florida really mean by this? Do they intend to utilize synthetic biology, for example, to artificially evolve humans from chimpanzee DNA? After all, the first comprehensive comparison of the genetic blueprints of humans and chimpanzees shows these primates share a perfect identity with 96 percent of human DNA sequences. [Nature Sept. 1, 2005]

Indeed, the discovery of DNA by James Watson and Francis Crick in 1953 was claimed to be the very mechanism behind Darwinian evolution. [Nature April 25, 1953, pp. 737—738, Nature May 30, 1953, pp. 964—967] Watson and Crick claimed their objective was to dethrone the traditional theory that a Creator produced life and to prove that life was created and controlled by DNA. The discovery of DNA was even called “the eighth day of creation.” [Judson, Horace Freeland, The Eighth Day of Creation: The Makers of the Revolution in Biology. Simon and Schuster, New York, 1979] Francis Crick, in an interview in 2003, said his distaste for religion was one of his prime motives in the work that led to the sensational 1953 discovery. “The god hypothesis is rather discredited,” said Crick. [Telegraph (London), March 20, 2003]

The problem has been that substitutions of new proteins that occur over time within the nucleotide ladder that comprise genes have never been able to demonstrate the production of a new species. Alterations in DNA describe traits and natural variation, such as coloration of butterfly wings or the differences in bird beaks noted by Charles Darwin during this stay in the Galpagos Islands in the 1800s. Mendelian genetics is often inappropriately portrayed as evidence of Darwinian evolution. Possibly synthetic biologists hope to prove they can create life and conclusively demonstrate evolution for the first time.

Recalling the Miller/Urey experiment

Synthetic biology’s objective, to “create life,” harks back to the laboratory experiment of Stanley L. Miller and Harold C. Urey in 1953 at the University of Chicago. Miller and Urey attempted to create the building blocks of life, amino acids, from a mixture of gases (ammonia, methane, hydrogen) and water, stimulated by an electric current that simulated atmospheric lightning, all believed to be common on the early earth. Their experiment, to re-create life’s building blocks from a “primordial soup,” was a flop and is often considered scientific mythology, since even if organic compounds could be created and real life forms emanate, a high methane-ammonia environment would have killed any living matter. [Science July 31, 130: 245—512, 1959] Nonetheless, the University of Chicago celebrated the 50th anniversary of the Miller/Urey experiment in 2003. Oddly, modern biology has never repeated the Miller/Urey experiment to verify its conclusions.

A different kind of genetic playground

There is a difference between genetic engineering and synthetic biology. The former involves insertion of existing genes into another species. For example, glow-in-the-dark fish have been created by insertion of a gene that produces a fluorescent chemical in their skin.

What synthetic biologists propose is to create novel genomes from a set of genetic parts. They want to create genes that don’t as yet exist in nature, and they can’t be sure how they will work until till implant them into living systems.

For now, synthetic biologists are limited to redesigning organisms with small genomes, like Mycoplasma genitalium which has the smallest known bacterial genome (482 protein-coding genes). But this is where the going gets worrisome.

The easiest area of biological manipulation is viruses. These are extremely small and simple life-forms, made merely of a protein shell and a genome. A virus reproduces by inserting its genome into the cells of other life-forms. As those cells duplicate, so does the virus. For example, scientists at the Centers for Disease Control and Prevention have synthesized the Spanish flu virus, responsible for the 1918 flu pandemic. They have been able to alter its genome and make it 39,000 times more virulent than any other flu virus! [Science (T. M. Tumpey et al.) 310, 77—80; 2005] What if this virus escapes from the laboratory?

Unpredictability

Synthetic biology is like designing a gun that will fire in unknown directions. Jonathan B. Tucker and Raymond A. Zilinskas, writing in New Atlantis, state that bioengineered systems remain “noisy,” that is, unpredictable. They quote Drew Endy of MIT who says synthetic biology is as yet unable to predict accurately how a new genetic circuit will behave inside a living cell. Synthetic biologists propose to create life forms de novo, that is, for the first time. There is no animal model where these new biological systems can be tested that can predict how it might behave in humans.

Public more concerned about lab scientists than biological terrorists

Markus Schmidt of Austria, writing in Nature Magazine, says the public is more fearful that the potentially troublesome lifeforms will be accidentally released from laboratories than they are concerned that some biological terrorist will unleash them for nefarious purposes. [Nature 441: June 29, 2006]

The most likely misapplication of synthetic biology involves the re-creation of known pathogenic viruses in the laboratory. These viruses could be a problem even if a person is genetically resistant and has been recently immunized.

Viruses have escaped from high bio-security labs. In 2003 a SARS virus escaped accidentally from a level-3 bio-security lab in Singapore, and in 2004 two further escapes occurred from such labs in Beijing. [Nature 437, 794—795 — 6 October 2005]

The recent anthrax attack by postal delivery was genetically tracked back to a strain developed at a military laboratory at the US Army Medical Research Institute for Infectious Diseases at Fort Detrick (USAMRIID), Maryland. [New Scientist news service, May 9, 2002] The investigation stopped there and proceeded no further.

Nature Magazine says “the ability of human societies to modify and transform biological systems will increase more in this century than it has in the hundred centuries since the dawn of agriculture.” [Nature 441, May 25, 2006] What are the chances a lethal virus will escape? It’s enough of an imagined nightmare for some biologists to demand that all such experiments be abandoned. Why take the chance, they ask?

Blame it on biohackers

Who is thinking of using synthetic biology — the “good guys” or the “bad guys?” Well, it’s not quite so easy to stereotype biological terrorists as being from Al Qaeda. News reports already want to blame any future release of synthetic life forms on “biohackers,” whoever that might be. [EE Times: Experts worry that synthetic biology may spawn biohackers, June 29, 2006] Actually, as previously stated, synthetic biology’s new life forms could find their way outside the laboratory, not by intent, but by mistake.

An article in Arms Control Today says: “Living synthetic cells will likely be made in the next decade; synthetic pathogens more effective than wild or genetically engineered natural pathogens will be possible sometime thereafter… Such synthetic cellular pathogens could be designed to be contagious or lethal or disabling.” [New Atlantis, Spring 2006] Notice this statement emanates from a military magazine, talking about biological warfare, not from a scientific journal talking about genetics being used to improve human life. The potential negative and harmful aspects of genetic engineering far outweigh any imagined benefits. Hundreds of genetic breakthroughs that would benefit mankind could be negated by one slip-up in a laboratory.

The initial demonstration project

In order to usher in synthetic biology and gain public approval, the initial showcased project is to develop a synthetic form of artemisinin, a molecule produced by the wormwood plant that naturally grows in Southeast Asia. While artemisinin is a very cheap remedy for malaria, synthetic biologists claim it is still costly (estimated cost of $1 billion to supply 70% of malaria victims worldwide), so they want to make it synthetically.

The Bill & Melinda Gates Foundation has released a $42.5 million grant to produce synthetic artemisinin. But this is not true synthetic biology. They would be creating the same molecule. It’s a covert way of gaining public acceptance for things to come under the banner of synthetic biology. Furthermore, the Bill & Melinda Gates Foundation is looking more like a non-profit front for R&D of vaccines and medicines that will eventually make billions of dollars on a worldwide scale.

Two courses

Consider two courses for synthetic biology. One is the current prevailing agenda to limit the size of human populations. Another is the prolongation of life.

Let’s consider the second use of synthetic biology first — to prolong the human life span. One way biologists could do this is to re-insert into human fertilized ova (eggs) the gene sequence for synthesis of an enzyme called gulonolactone oxidase (GLO), so that human offspring can continually synthesize vitamin C as most other mammals do.

This should be a priority among biologists since humans carry a dysfunctional gene for this enzyme, which disables the synthesis of vitamin C in the liver, making humans totally reliant upon paltry dietary doses of vitamin C to prevent scurvy. Surprisingly, there are only 142 published reports on GLO in the expansive and growing National Library of Medicine database. Biologists have demonstrated little interest in this topic.

Humans have been described as a mutant species because of their inability to produce vitamin C. Most mammals have the intact gene for GLO synthesis and produce generous daily amounts of the liver metabolite ascorbate (vitamin C), about 20 milligrams per pound of body weight (equivalent to 3200 milligrams for a 160-pound/70-kilogram human). The restoration of this missing hormone/vitamin was proposed by Irwin Stone in the 1970s to create “a new and more robust, longer-living, tough human sub-species.” [Medical Hypotheses 5: 711—21, 1979]

Four enzymes are required for the conversion of blood sugar into ascorbate (vitamin C). Long ago in human history the gene that controls the fourth enzyme, gulonolactone oxidase, fell into disrepair. The injection of the GLO enzyme into guinea pigs, which suffer the same predicament as humans and cannot synthesize ascorbate, produces vitamin C. [Nutrition Reviews 1982 Oct; 40(10): 310—1] The effects of this mutation and vitamin deficiency are not solely limited to symptoms of overt scurvy (bleeding gums, sore joints, fatigue, poor wound healing). For example, without the provision of supplemental vitamin C, ~800 milligram human equivalent in a guinea pig, this animal will invariably develop cardiovascular disease and die prematurely.

The whole structure of the human GLO gene, which is similar in structure and origin to a gene in another species, has been disclosed by a computer-assisted search. Geneticists at Wakayama University in Japan know how to correct this genetic error.

Here is their description of the problem:

Only five exons (the protein coding DNA sequence of a gene), as compared to 12 exons constituting the functional rat GLO gene, remain in the human genome. A comparison of these exons with those of their functional counterparts in rats shows that there are two single nucleotide deletions (a nucleotide is a subunit of DNA as adenine, guanine, thymine, or cytosine), one triple nucleotide deletion, and one single nucleotide insertion in the human sequence. When compared in terms of codons (a specific sequence of three DNA bases within a gene), the human sequence has a deletion of a single amino acid, two stop codons, and two aberrant codons missing one nucleotide besides many amino acid substitutions. [Journal Nutrition Science Vitaminology 49: 315—19, 2003]

Furthermore, researchers at Kyoto University in Japan have successfully inserted the missing or dysfunctional GLO gene into fertilized eggs of scurvy-prone medaka fish, producing offspring that can synthesize vitamin C. [Biochemical Biophysical Research Communications 223: 650—53, 1996]

So why is there no priority among synthetic biologists to restore the major human biological flaw that has plagued mankind for centuries? The lack of expressed enthusiasm for the re-insertion of a functional GLO gene into the human genome goes unexplained. Maybe it’s because the loss of the GLO gene does not fit preconceived Darwinian theories, that mankind progressively evolved from lower species. This gene mutation would have made Homo sapiens less able to survive. Who really knows why this main concern hasn’t taken precedence within the ranks of synthetic biologists? It is believed the restoration of the GLO gene would prolong human life by many decades over and above current life expectancy. Possibly the prevailing agenda to control the size of the world’s human population would explain the absence of a GLO gene insertion project from the drawing boards of biologists.

Course No. 2 for synthetic biology

Now ponder how synthetic biology could be employed to address the population control agenda. The “accidental” development of a deadly virus that escapes from a lab would be one scenario that comes to mind. It has been said that nature once kept the size of human populations under control by periodically unleashing plagues, and that diseases of old need to be re-introduced, in keeping with the Darwinian theory of “survival of the fittest.” It is interesting to note that once humans gained the knowledge of how to manipulate the genome of pathogenic germs, we hear of retroviruses and mutated viruses that can sweep the earth and potentially kill millions, maybe billions. There is no natural mutation that explains why viruses are jumping from animals to humans for the first time in history.

Covert population control efforts already underway

Massive overt efforts to control world population size are underway, which include birth control, delay of marriage, acceptance of gay marriage, limitation of family size, abortion, greater independence of females, etc. However, there is suspicion that covert efforts to control population size are already underway. Why do fertility clinics abound today when they were never needed decades ago?

For example, the recent realization that cholesterol reduction doesn’t significantly improve life expectancy causes one to wonder why cholesterol control is such a widely promoted public agenda. [Journal Hypertension 23:1803—8, 2005] It may surprise you to learn that a report in the Journal of the Pharmaceutical Society of Japan calls for the abandonment of the cholesterol theory of heart disease. [Journal Pharmaceutical Society Japan -YAKUGAKU ZASSHI, Volume 125 (11), pages 833—852, 2005]

Dietary fat and cholesterol are a precursor to the synthesis of estrogen and testosterone, sex hormones required for fertility and virility. Female mice that have altered forms of HDL cholesterol are infertile. [Journal Clinical Investigation 2001 Dec; 108(11): 1717—22] Lowering cholesterol may lower hormone levels. Is the public program to control cholesterol, even among fertile young adults who are at little risk for cardiovascular disease, just a hidden population control program?

The effort to insert fluoride into public drinking water supplies may also be a covert population control method.

The fact that credible experts have voiced their scientific objections to fluoridation, that European nations forbid fluoridation of water supplies, and the fact that persons who have grown up with fluoridated water have, on the average, only 1/2 of one filling less per lifetime than people who did not drink fluoridated water [Chemical and Engineering News, May 8, 1989], causes one to ask, why does the U.S. fluoridate drinking water supplies? Scientific objections to fluoridation by David R. Hill, Professor Emeritus, The University of Calgary, Alberta, Canada, and Robert J. Carton, PhD, former EPA scientist can be viewed online.

A single micro-dose of fluoride injected into adult male albino rats causes arrest of sperm production and absence of sperm in the testes. [Reproductive Toxicology 1991; 5(6): 505—12] However, the mating, fertility and survival indices of rodents are not affected by high levels of fluoride in drinking water. [Food Chemistry Toxicology 2001 Jun; 39(6): 601—13] But rodents synthesize their own vitamin C as a hormone; humans do not, and thus have natural protection against the deleterious effects of fluoride. The provision of supplemental vitamin C reverses adverse effects of fluoride on male sperm. [International Journal Fertility Menopausal Studies 1994 Nov-Dec; 39 (6): 337—46]

Covert population control efforts may explain the current effort to limit dosage of vitamins in dietary supplements (CODEX-World Health Organization). Decreased levels of vitamin C impair the production of sperm in human males. [West African Journal Medicine 2004 Oct-Dec; 23(4): 290—3] Vitamin supplements prolong the period of fertility in animals. [British Poultry Science 2005 Jun; 46(3): 366—73] Limitations on dosage of vitamins in food supplements could adversely affect fertility rates in human populations.

Would synthetic biology similarly be employed in covert attempts to control the size of human populations?

Creating new life

To many people, the idea of creating life in the laboratory seems like science fiction. Yet some synthetic scientists now claim they are on the verge of doing it. Assume for a moment that, in the interest of basic science, synthetic biologists want only to test hypotheses to confirm the theory of Darwinian evolution. This sounds innocent enough. Yet, even if synthetic biologists can create a new virus de novo, that is, from scratch, this still does not create a complex life form nor explain how amino acids (proteins) came to be formed or arranged into DNA.

Paul Davies is a visiting professor at Imperial College Life, described the challenge in a 2002 issue of the Guardian (UK). Davies says life, as we now know it, is not magic matter. It isn’t something that can be incubated in chemistry labs. “It can’t be conjured up by infusing matter with energy, such as a bolt of electricity, à la Dr Frankenstein.” No life force can be added to molecules to create life.

Professor Davies explains it this way:

“Instead, the living cell is best thought of as a supercomputer — an information processing and replicating system of astonishing complexity. DNA is not a special life-giving molecule, but a genetic databank that transmits its information using a mathematical code. Most of the workings of the cell are best described, not in terms of material stuff — hardware — but as information, or software. Trying to make life by mixing chemicals in a test tube is like soldering switches and wires in an attempt to produce Windows 98. It won’t work because it addresses the problem at the wrong conceptual level.”

Bill Gates, founder of Microsoft, commented that “DNA is like a software program, only much more complex than anything we’ve ever devised.”

In 2002 Craig Venter, a pioneer involved in the human genome project, announced his intention to create a brand new life form. Venter plans to strip down and reconstruct the genome of Mycoplasma genitalium, a primitive microbe that inhabits the genital tract.

Professor Davies suggests we don’t hold our breath over this. He says:

“But this isn’t making life so much as rearranging it. Even a simple bacterium is a vast assemblage of intricately crafted molecules, many of them elaborately customized. Although those specialized molecules are not themselves living, they are the products of living things. Scientists make use of them in their microbial tinkering. In other words, they use the products of living organisms to re-make living organisms. They remain a long way from being able to put together a living cell from scratch.”

Davies ends his paper by asking: “How did nature fabricate the world’s first digital information processor — the original living cell — from the blind chaos of blundering molecules? How did molecular hardware get to write its own software?”

Maybe the question of the origin of life is beyond the reach of modern biology. Long ago the author of the Book of Ecclesiastes (3:11) said: “No man can find out the work that God maketh from the beginning to the end.” Maybe we will never know.

Bill Sardi [send him mail] is a consumer advocate and health journalist, writing from San Dimas, California. He offers a free downloadable book, The Collapse of Conventional Medicine, at his website.

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