Researchers Use Genetic Engineering to Wipe Out Malaria-Carrying Mosquitoes in Lab

In September,  Nature Biotechnology published a paper by researchers describing their efforts to use CRISPR-Cas9 in a laboratory setting to prevent reproduction in a population of mosquitoes that transmit malaria to human beings,

In the human malaria vector Anopheles gambiae, the gene doublesex (Agdsx) encodes two alternatively spliced transcripts, dsx-female (AgdsxF) and dsx-male (AgdsxM), that control differentiation of the two sexes. The female transcript, unlike the male, contains an exon (exon 5) whose sequence is highly conserved in all Anopheles mosquitoes so far analyzed. We found that CRISPR–Cas9-targeted disruption of the intron 4–exon 5 boundary aimed at blocking the formation of functional AgdsxF did not affect male development or fertility, whereas females homozygous for the disrupted allele showed an intersex phenotype and complete sterility. A CRISPR–Cas9 gene drive construct targeting this same sequence spread rapidly in caged mosquitoes, reaching 100% prevalence within 7–11 generations while progressively reducing egg production to the point of total population collapse. Owing to functional constraint of the target sequence, no selection of alleles resistant to the gene drive occurred in these laboratory experiments. Cas9-resistant variants arose in each generation at the target site but did not block the spread of the drive

The Vatican’s ‘Dignitas Personae’

The Center for Inquiry issued a press release in mid-December attacking the Catholic Church’s Dignitas Personae, largely on abortion-related grounds (the Catholic Church, not surprisingly, is still against it). According to CFI,

The Center for Inquiry, a think tank headquartered in Amherst, New York that supports research on bioethical questions, deplores the Vatican’s pronouncement. The Vatican’s position has no justification other than religious doctrine, according to the Center for Inquiry, and may have a serious adverse effect on scientific research and the development of medical therapies.

“I regret the renewed effort by the Vatican to censor—indeed prohibit—research in reproductive science,” said Paul Kurtz, chairman and founder of the Center for Inquiry. “Do we have to wage the Galileo battle again? The Vatican claims that their objections are “moral,” but they are based on a theological doctrine that a formless fertilized egg is a full human being, a position which most scientists reject.” Kurtz says there is a need to defend freedom of scientific research and the positive good that can ensue for countless numbers of infertile couples. “The effort to curtail stem cell research is especially disturbing in the view of the possible beneficent results for improving human health,” he said.

The Vatican has focused on commonplace scientific technologies used in the United States and elsewhere, which the Church believes demean human “dignity,” and bring humans perilously close to “playing God.” The Church continues to hold steadfast to its key theological proclamation that “life begins at conception,” thereby rendering as “illicit” the use of embryos or fertilized eggs in research or otherwise, including IVF for married Catholic couples wishing to conceive.

Dr. Ronald A. Lindsay, president and CEO of the Center for Inquiry (and author of the book Future Bioethics: Overcoming Taboos, Myths, and Dogmas) said that “the Vatican has once again manifested its regrettable preference for religious doctrine over science. Until roughly fourteen days after conception, one cannot even meaningfully refer to the embryo as an individual, let alone the equivalent of an adult human, since both twinning and fusion are possible until that point.” Lindsay added that the Vatican’s rejection of IVF on the ground that it results in the discarding of embryos is especially ironic since from 60 to 80 percent of embryos conceived “naturally” are spontaneously aborted. “If the Vatican wants to prevent embryos from ‘dying,’ then they will have to instruct couples to avoid sex completely.

Dignitas Personae is interesting both for the technologies it deplores and the “logic” it bases those judgments upon.

For example, consider intracytoplasmic sperm injection — a procedure whereby a single sperm is injected into an egg to fertilize it. ICSI has a number of purposes, including being used in to overcome male infertility. Dignitas Personae objects to ICSI because it separates procreation from the sexual act,

Just as in general with in vitro fertilization, of which it is a variety, ICSI is intrinsically illicit:  it causes a complete separation between procreation and the conjugal act. Indeed ICSI takes place “outside the bodies of the couple through actions of third parties whose competence and technical activity determine the success of the procedure. Such fertilization entrusts the life and identity of the embryo into the power of doctors and biologists and establishes the domination of technology over the origin and destiny of the human person. Such a relationship of domination is in itself contrary to the dignity and equality that must be common to parents and children. Conception in vitro is the result of the technical action which presides over fertilization. Such fertilization is neither in fact achieved nor positively willed as the expression and fruit of a specific act of the conjugal union”.

Similarly, the objection to genetic engineering comes down to vague and poorly defined concerns,

27. The question of using genetic engineering for purposes other than medical treatment also calls for consideration. Some have imagined the possibility of using techniques of genetic engineering to introduce alterations with the presumed aim of improving and strengthening the gene pool. Some of these proposals exhibit a certain dissatisfaction or even rejection of the value of the human being as a finite creature and person. Apart from technical difficulties and the real and potential risks involved, such manipulation would promote a eugenic mentality and would lead to indirect social stigma with regard to people who lack certain qualities, while privileging qualities that happen to be appreciated by a certain culture or society; such qualities do not constitute what is specifically human. This would be in contrast with the fundamental truth of the equality of all human beings which is expressed in the principle of justice, the violation of which, in the long run, would harm peaceful coexistence among individuals. Furthermore, one wonders who would be able to establish which modifications were to be held as positive and which not, or what limits should be placed on individual requests for improvement since it would be materially impossible to fulfil the wishes of every single person. Any conceivable response to these questions would, however, derive from arbitrary and questionable criteria. All of this leads to the conclusion that the prospect of such an intervention would end sooner or later by harming the common good, by favouring the will of some over the freedom of others. Finally it must also be noted that in the attempt to create a new type of human being one can recognize an ideological element in which man tries to take the place of his Creator.

In stating the ethical negativity of these kinds of interventions which imply an unjust domination of man over man, the Church also recalls the need to return to an attitude of care for people and of education in accepting human life in its concrete historical finite nature.

Leaving for the moment the absurdity of the Catholic Church being suddenly concerned about the “unjust domination of man over man”, the concern about “man trying to take the place of the Creator” is telling.

Of course human beings wouldn’t have to take that route if the Creator hadn’t done such a piss poor job of it in the first place. The Church’s position is that we should simply accept our numerous defects — such as the ridiculously short lifespan — as “God given” and simply not attempt to improve our arbitrary genetic heritage.

European Patent Office Upholds Mouse Patent

In July the European Patent Office upheld Harvard University’s patent on a genetically altered mouse. The EPO did modify the patent so that it applied only to “transgenic mice” rather than the original language of the patent which covered “transgenic rodents.”

In a press release announcing the decision, the EPO said,

As a result of an appeal decision, European patent EP 0 169 672, better-known as the “Oncomouse” patent, has been further restricted.

In 1985 the President and Fellows of Harvard College, Cambridge, Massachusetts, USA, applied for a European patent entitled “Method for producing transgenic animals”. The patent was granted in May 1992 in respect of “non-human mammalian animals” for eleven member states of the European Patent Organisation.

Seventeen oppositions against the patent, filed in 1992 and 1993, led to the decision in November 2001 to maintain the patent in respect of “transgenic rodents”. Several appeals against that decision lodged in March 2003 were heard by the Technical Board of Appeal which decided to restrict the patent further to “transgenic mice”.

Greenpeace and a number of other organizations had filed the challenges, seeking to have the EPO overturn the validity of patenting animals altogether. Jan Creamer of Great Britain’s National Anti-Vivisection Society said of the ruling,

. . .patenting life should be wrong. You’re not producing a product that will make a difference.

Harvard University’s Philip Leder, who was one of the co-creator’s of the Oncomouse, disagreed, telling The Scientist,

This is the organism that has the greatest utility. I’m pleased to have the matter resolved.

Dupont, which holds the licensing rights to the mouse, has issued 170 licenses for academic research on the mouse. It charges licensing fees for commercial uses of the patented mouse.

Source:

EPO restricts OncoMouse patent. Paula Park, The Scientist, July 26, 2004.

Technical Board of Appeal restricts “Oncomouse” patent. Press Release, European Patent Office, July 6, 2004.

Europe upholds Harvard Mouse patent. Associated Press, July 7, 2004.

Biotech Company Creates Cattle that Express Human Proteins

Biotechnology firm Hematech this month reported that it has succeeded in creating genetically modified calves that carry human genes.

The company inserts the gene for human heavy and light chain antibody genes into bovine fetal fibroblast cells. This is accomplished by knocking out both copies of the bovine immunoglobulin gene to reduce the level of bovine antibodies circulating in the blood of the animals so that detectable levels of human antibodies remain.

Another problem the company will have to face is genetically engineering the animals to prevent the possibility of transmitting prion diseases such as Mad Cow’s. The company plans on creating genetically modified cattle that lack the genes necessary to produce prion proteins. Hematech CEO James Barton told InPharma.Com,

If live animals are produced form these embryos [lacking the genes necessary to produce prion proteins] they will be prion free and thus unable to contract mad cow disease. These animals will be ideal for the production of the company’s fully human polyclonal antibodies.

Details of Hematech’s research in knocking out the bovine immunoglobulin gene is scheduled to be published in Nature Genetics.

Source:

Cattle antibody production moves a step closer. InPharma.Com, June 3, 2004.

Mayo Clinic Researchers Observe Fusing of Human, Non-Human Cells in Living Body

The Mayo Clinic announced on January 8 that its genomics researchers demonstrated for the first time that human and non-human cells could naturally mix their genetic material in a living body. According to a press release from the Mayo Clinic announcing the discovery,

In the research reported today, Mayo Clinic investigators implanted human blood stem cells into fetal pigs. The pigs look and behave like normal pigs. But cellular analysis shows they have some human blood cells, as well as some cells that are hybrid — part human, part pig — in their blood, and in some of their organs. Molecular examination shows the hybrid cells have one nucleus with genetic materials from both the human and the pig. Importantly, the hybrid cells were found to have the porcine endogenous retrovirus, a distant cousin of HIV, and to be able to transmit that virus to uninfected human cells.

Jeffrey Platt, director of the Mayo Clinic Transplantation Biology Program, said the surprising results may help explain how some viruses can jump so quickly between humans and non-humans. In a press release statement, Platt said,

What we found was completely unexpected. This observation helps explain how a retrovirus can jump from one species to another — and that may speed discovery about the origin of diseases such as AIDS and SARS. The discovery may also help explain how cells in the circulation may become part of the solid tissue.

The Mayo Clinic findings will be published in March in the online Express edition of the Federation of American Societies for Experimental Biology Journal.

Source:

Mayo researchers observe genetic fusion of human, animal cells — may help explain origins of AIDS. Press Release, Mayo Clinic, January 8, 2004.

Singapore Researchers Working on Edible Zebrafish Vaccine

Researchers at the National University of Singapore reported in September that they had produced genetically modified zebrafish that produce a vaccine for Hepatitis B in their muscles. Such research could one day pave the way for a cheaply produced, edible vaccine.

Leader researcher and zebrafish Gong Zhiyan concedes that there are still many unknowns about using genetically modified animals like this to produce vaccines. Zhiyan told The BBC,

We haven’t reached the stage yet where we know how many fish you would have to eat for a correct dose of vaccine, but based on the high levels of the protein they produce, it shouldn’t be much.

In addition, the vaccine would have to survive the passage through the digestion system and into the human bloodstream in a usable way.

To that end, the next step in this line of research will be producing and feeding these vaccine-producing zebrafish to animals to see if they confer protection from Hepatitis B when eaten.

Sources:

Edible vaccines ‘could end jabs’. The BBC, September 15, 2003.