Personal website of João Pedro de Magalhães
Home    Thoughts

Genetic Engineering

"Nothing is too wonderful to be true." — Michael Faraday

Modern molecular genetics has revolutionized medicine and our knowledge of ourselves. As a scientist working on the genetics and genomics of aging, it is my obligation to discuss the power and limitations of modern genetics. I also like to dream about the most revolutionary, and often most controversial, applications of genetic engineering and these are discussed below.

Introduction

Since Mendel's experiments on heredity and the identification of the DNA as the genetic material, we started to know how and why we are like we are, we started to understand what makes human beings human. The DNA contains genes, passed to us in roughly equal proportions from our parents, that are like the instructions of a computer program running within us, inside each and every cell that makes up our body. The whole program, the complete DNA, makes up the genome, which contains not only all genes but large empty areas that are basically junk. Genes by and large encode proteins, which are the building blocks of our bodies. Differences in genes between individuals determine, for instance, gender, eye color and susceptibility to certain diseases. To a large degree we are what our genes code us to be.

The DNA is a molecular chain physically located in chromosomes, structures present in the nucleus of cells that compose our bodies. Genes are encoded by the DNA and specify how and when to build proteins which then act as molecular machines. These molecular machines interact in complex networks to perform most vital functions in cells. The communities of cells, through complex interactions, then give rise to animals, including human beings. Picture from genomics.energy.gov.

In simple terms, genetic engineering (GE) is the ability to manipulate the genes of an organism to produce a given protein or obtain organisms that have a given trait. The first big success of GE was the production of insulin by genetically modified bacteria. It showed the medical, economical, and industrial possibilities of this technology. Like a pyramid buried in the sands of the desert, the possibilities and uses of GE were being uncovered. Thanks to refined techniques in molecular genetics and recombinant DNA techniques, its uses soon started to be employed in a vast array of areas:

• Pharmaceuticals: producing monoclonal antibodies, antibiotics, vaccines, interferon, and many other proteins with pharmaceutical value.
• Agriculture: modifying plants to become more resistant to pathogens and to harsh environments, or producing insecticides.
• The food industry: breeding animals has been done for thousands of years, but GE allows the creation of livestock with unprecedented precision in a shorter time. For instance, cattle can be engineered to be bigger, with higher reproduction rates, of better quality, etc. Stemming from agriculture, it is possible to modify certain foods, such as fruits and livestock, in terms of sweetness, color, and even nutritional value -- e.g., developing animals whose meat has less fat.
• Industry: using microorganisms to produce all sorts of molecules and optimizing molecules by mutagenesis and computational models that can then be produced by genetically-modified microorganisms like bacteria.
• Environmental applications: bioremediation by creating and optimizing bacteria capable of degrading xenobiotics.

The greatest applications of genetics, however, are in medicine. Recent advances in genome sequencing, bioinformatics and genomics are driving sequencing costs down to the point that sequencing the genome of everyone will soon be cost-effective. This will increase our knowledge of life and of the genetics of disease even further. Knowing which gene, which piece of the genetic code is responsible -- or at least a risk factor -- for a given disease allows physicians to diagnose a variety of diseases and tailor treatments to each patient in the emerging area of personalized medicine. It also allows scientists the opportunity to understand how diseases occur and eventually develop treatments, for example by targeting disease-associated gene variants. A significant part of modern biomedical research is conducted based on genetics and GE. For instance, in my field of aging research, we can alter the pace of aging in animal models by modifying single genes which allows us to study why we age and how can we treat the diseases of old-age. At least until nanotechnology arrives, GE is the ultimate biotool.

Evolving Beyond Humans

Perfection is something that doesn't exist in nature. You and me are no different. We suffer from painful and horrible diseases, we can die for the most trivial causes, we will inevitably die of aging, etc. Yet we can, at least in theory, change all that. We can change the tyranny of the genes and become better than we are now.

The possibilities for applying GE to change the human genome are immense: there are genes that offer protection against diseases such as cancer and AIDS, genes that code enhanced senses and intelligence, anything we can imagine. For example, many animals have skills we do not possess like limb regeneration. While much work remains to identify those genes, in theory, it is possible in the future to incorporate such functions into humans. In addition, as computers evolve, we may be able to design proteins in computers to suit one's individual needs. For instance, it may be possible in the foreseeable future to go to the doctor and have a gene "inserted" that gives rise to a stronger immune system.

At present, technology to upgrade our genes is still in its infancy and it is typically very difficult to change a gene in an adult human. Progress has been made in the areas of stem cells and tissue engineering by extracting cells from the patient, genetically engineer them and then insert them into the patient with the gene of interest modified. Another technology is gene therapy, which usually involves injecting modified viruses into patients that then deliver the gene of interest into the patient's cells. For example, Nadia Rosenthal and colleagues have developed a gene therapy method that improves age-related muscle degeneration by using a virus to augment the expression -- i.e., the production -- of a gene called IGF1. Side-effects such as strong immune responses and in some cases cancer remain as obstacles that must be solved before gene therapy can have widespread applications in the clinic.

One more ambitious and polemic technique is GE on germinal tissues, which consists of the ability to change one's genes in a way that his/her offspring will be affected. This can and must -- with current knowledge -- be done in the early stages of development. This technique is already used in many model organisms, including primates such as rhesus monkeys, but its use on humans is forbidden by most countries' laws. The prohibition is mostly based on the health risks involved. For example, germinal GE on mice is not particularly effective and many things can go wrong. It also makes sense, however, to continue research and attempt to develop a safe GE for human applications. There are cases of patients with severe genetic diseases or that are hosts for genetic diseases and whose children would also have a high risk of having such diseases. GE can provide a solution to these cases by correcting the gene(s) associated with the disease.

In 2001, the first genetically altered babies were born. A bit of background is necessary, though. The large majority of genes are in the nucleus of cells, called the nuclear genome, which is inherited from both the mother and father in approximately equal quantities. A tiny fraction of the genome is in mitochondria, small cellular organelles with their own genome. This genome, called the mitochondrial DNA, is inherited only from the mother. In the 2001 case, because the mother's mitochondrial DNA had errors, researchers used the mitochondrial DNA from a donor woman and thus the babies had half of their nuclear genome from their father, half from their mother, and the mitochondrial DNA of another woman. This was the first case of a human germline genetic modification. The babies were healthy.

There are thousands of genetic diseases that are encoded by the nuclear genome¹, such as the Down's syndrome and horrible life-threatening diseases like Tay-Sachs syndrome, cystic fibrosis, and Gaucher's disease. For now, prevention is the only choice. Pregnant women can employ genetic counseling and screening techniques such as amniocentesis, which involves testing fetal cells for genetic diseases. A more complicated option is pre-implantation genetic diagnosis (PGD). In this technique, used to create what is often called a "designer baby," an embryo is created by in-vitro fertilization (IVF) and tested for genetic diseases and genomic imbalances that can cause problems to the child. This technique allows for the selection of healthy babies, but also to create a new baby to treat an older sick sibling. Similarly, it is possible to select for certain traits, such as eye color or the sex of babies, though this is forbidden in many countries.

These techniques raise several ethical questions and have been a heated topic of debate in bioethics. The main reason why "designer babies" are polemic and opposed by many is that embryos are destroyed when they are unsuitable. Although such embryos typically have less than 10 cells, pro-life advocates who believe that life begins at conception hence oppose this research because they believe it is killing people.

As a transhumanist, I defend my right to change and upgrade my body as I please. I also defend that if I wish to have children with upgraded brains or certain beneficial features, I should be allowed to, assuming the method is proven safe of course -- otherwise I wouldn't be interested in it anyway. The issue of whether embryos are humans beings is beyond the focus of this essay. Nonetheless, I do not think that an embryo without a circulatory system, without a nervous system, without any evidence of a mind or of consciousness, cannot be considered a person.

The next step in "designer babies" is to use GE to correct genetic diseases in the embryo. If we spend millions trying to cure diseases like asthma, baldness, cancer, why shouldn't we prevent these diseases before we are even born? Admittedly, the technology is not safe yet, but it will likely be one day not far into the future. Assuming the procedure is safe, I see no reason to stop someone from not only eliminating genetic errors but improving his/her children from a functional and even an aesthetic point a view.

Some people argue that germinal GE will reduce the human species to only a few types of individuals, which I doubt. How many beautiful people do you know? I think there are millions of beautiful people each of them with their own individuality. The combinations are endless. Germinal tissue GE would only eliminate the ugly extremes but it would not decrease human diversity. Of course it would be necessary to protect celebrities from having their genes cloned, for individuals should have their personal rights protected. It also has been argued that GE can aggravate social differences, which is possible. But just because there are people in the world who can't afford to have heart surgery that doesn't mean we should eradicate it and stop saving lives.

Importantly, germinal GE would allow for the evolution of the human species. I should emphasize that this is not related to eugenics but with individual evolution only. As mentioned above, I defend only the right to upgrade myself and my children, never impose my will on others. We can evolve beyond our natural limitations using genetics. As I mention elsewhere, nature made us to suffer and die; it's our duty to fight and overpower nature and become masters of our destiny. Nonetheless, and contrary to most religious extremists who wish to impose their views on others, I think these issues should always be an individual decision.

Upgrading our genome is the future. Of course we need to be cautious as there are still many technical problems to solve and we must be confident that these procedures are safe. But new techniques are being developed and we can expect major progress in the near future. In our constant and ever lasting search for perfection we must change the environment that surrounds us but we must also change ourselves.

The 47^th Chromosome

Each chromosome contains part of the genetic code. Above are my 46 chromosomes.

The 47th chromosome, also called techno-chromosome, is a theoretical concept that proposes adding a new chromosome, or more likely a pair of chromosomes, to our current set of 46 chromosomes. This would allow us to include all the changes we desire without the danger of creating genetic imbalances by changing our current chromosomes. Engineered artificial chromosomes that can be passed into the progeny of mice have been developed, and there are attempts to expand this research into humans as cell-mediated gene therapy and stem cell therapy, so this is not science fiction.

Forecasting the future isn't easy. Nevertheless, below is a brief vision of the future composed of some of the most ambitious ideas for using GE I've come across:

• Many types of improvements can be made to our metabolism. Besides the obvious life-extension procedures, we might be able to turn ourselves more physically resistant in all sorts of manners. Making our skin and bones harder, making us stronger, improving our stamina, giving us super-intelligence, minimizing pain and overall optimizing our biochemistry.

• Many times, we have a disease but don't know about it until it's too late. If we can make the body have some sort of reaction when, hypothetically, a few cancer cells are present that would be a major breakthrough in medicine. The idea is to include certain enzymes that can be activated when genes associated with cancer are activated in cancer cells. They could produce a certain chemical compound that would, say, turn the cells pink or the urine green. This, of course, can be applied to many other diseases.

• An Israeli scientist, Ehud Shapiro, proposed the inclusion of tiny biological computers in cells to work as microscopic doctors. Advances in DNA computer technology have been amazing and perhaps DNA processing machinery can use DNA as a basic Turing machine that works as a computer. The computer can then be programmed to perform certain functions, namely, detecting, signaling, and treating pathologies.

• To incorporate in the genome genes that can offer protection during cryopreservation for long space trips.

• To include viruses, called bacteriophages, that attack bacteria and can then be produced by the immune system to attack pathogenic bacteria whenever necessary. Each bacteriophage would be specific for each bacterial strain or family and could be present in the blood at small concentrations when no infection was present.

• One ingenious idea is to encrypt the genome. Encrypting the genome is changing the DNA sequence that codes for a certain amino acid, the blocks from which proteins are built based on the information in the genes. The result would be a complete resistance to viruses because viruses use the body's DNA machinery; the viral DNA would code for the wrong amino acids and therefore would be inert. There is actually exciting work being done in synthetic biology by my former colleague Farren Isaacs who attempting to do this in bacteria.

Overall, the possibilities for improving the human condition are tantalizing. Much work remains to understand the function of our genes and how they interact with each other and with the environment, and such knowledge is key to develop effective therapies. Crucially, much works remains in developing the technologies to modify genes in adult humans with sufficient power and precision. Hence some of the applications described above are still decades away. Nonetheless, it is an exciting road ahead. Religious groups and conservatives will continue to oppose progress and technology but if GE improves human health and extends life then it will no doubt prevail and become widespread. After all, the use of anesthesia in child birth was opposed by religious groups and now is commonly used. Even forks were opposed by some religious clerics when they were first introduced. I am convinced that this century we will take control of our genes and of our bodies to help us live longer, healthier lives.

Sources and Links

¹ — Some researchers, like Paul Berg, actually claim that all diseases are genetic.

Brock, Thomas D.; "Biology of Microorganisms" (1997).

Glick, Bernard R. & Jack J. Pasternak; "Molecular Biotechnology: Principles and Applications of Recombinant DNA" (1998).

Griffiths, Anthony J. F. et al; "An Introduction to Genetic Analysis" (1996).

Lemoine, N. (editor); "Understanding Gene Therapy" (1999).

Lewin, Benjamin; "Genes VI" (1997).

Lyon, Jeff, Peter Gorner (Contributor); "Altered Fates: Gene Therapy and the Retooling of Human Life" (1996).

Nossal, G. J. V.; "Reshaping Life - Key Issues in Genetic Engineering" (1985 & 1989 versions).

Russo, Enzo, David Cove; "Genetic Engineering: Dreams and Nightmares" (1995).

Stock, Gregory; "Redesigning Humans: Our Inevitable Genetic Future" (2002).

Vogel, F. & Motulsky, A. G.; "Human Genetics: Problems and Approaches" (1997).

GeneWatch; website on the ethical issues and risks of genetic engineering.