Germline gene modification: the issues. (Book by Jennifer Doudna)

"And all long-term exercises of power, especially in breeding, must mean the power of early generations over later ones." - C. S. Lewis, The Abolition of Man 

I have recently read a book by Jennifer Doudna, entitled A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. There is a co-author, but it seems clear that most of what is said came from Doudna. As the Wikipedia puts it, "Doudna has been a leading figure in what is referred to as the 'CRISPR revolution' for her fundamental work and leadership in developing CRISPR-mediated genome editing." I would expect that she will be getting a Nobel Prize in the next year or so. (She is also part owner of a company which has, or is expected to commercialize these techniques.)

CRISPR stands for clustered regularly interspaced short palindromic repeats, [and] is a family of DNA sequences found within the genomes of ... organisms such as bacteria ... These sequences are derived from DNA fragments from viruses that have previously infected the [organisms] and are used to detect and destroy DNA from similar viruses during subsequent infections. Hence these sequences play a key role in the antiviral defense system of prokaryotes. (From the Wikipedia article on CRISPR.)

The discoveries of Doudna, and many others, have made it possible to use the CRISPR immune system of bacteria to make targeted changes in DNA. It's a little more complicated than this, but, basically, if you know the nucleotide sequence of the DNA you want to change, you can use CRISPR to delete as little as a single base pair, or to change small sections of DNA. The technique does not require lots of expensive equipment. This has made it possible to alter the genomes of laboratory organisms, domestic animals, crop plants, and even human cells. In a recent case, it may have been used to modify human embryos. A Chinese scientist claims to have modified twin girls so that they could not contract AIDS. The claim has been questioned, and the timing, if the report is correct, has been seriously questioned -- preliminary experiments, at least, should have been done. The Chinese government has acted to punish the scientist. Many people fear that we don't know enough about the safety of the CRISPR system. Could it be that other DNA can be altered, rather than the target, with unforseen consequences?

The book is well written, although there is a lot of name-dropping -- scientists Doudna has worked with. Documentation is good, and it is at the end of the book, where it doesn't interfere with the train of thought.

It is clear that Doudna believes that CRISPR should be used on humans, carefully, and after considerable thought and planning. (Lots of which we haven't done yet.) She even believes that, after considerable more study and experimentation, we (speaking for the majority) may come to accept alteration of germ cells in humans.

What's a germ cell? First, what isn't one? Almost all of our cells are somatic cells. That is, they are cells that do not become sperm or eggs. Somatic cells may be altered -- in fact are altered, all the time, by random mistakes in cell copying, or by agents like Ultraviolet light, or others that cause cancers. Or we remove billions of them when we take out an appendix, or some other part of us. But the offspring of people with changed somatic cells do not inherit these changes. I had a skin cancer removed from my face. If I were to get married, and my wife have a child, the child would not be more likely to have skin cancer than another baby born to a couple who had never had skin cancer. I had my tonsils out when I was a child, but my daughters were born with tonsils.

Germ cell alteration, changing the cells that produce sperm, or egg cells, would mean that an organism's offspring, for the forseeable future, would be different, in subtle or major ways, from what that organism was. And, eventually, that change might spread through an entire population, or an entire species, as more and more descendants of that organism appeared.

Why not encourage germ cell alteration? There are some possible objections:

It's unnatural. But so are lots of things that most of us take for granted, such as eyeglasses, Caesarean sections and other surgery, antibiotics made from fungi, artificial limbs, and much more, which are unnatural -- not the way things would be without deliberate action by humans. Unless there's some safety problem, such as if eyeglasses caused cancer, or the procedure or apparatus is prohibitively expensive, there doesn't seem to be a good reason to object to these types of things.

There was a time when the use of anesthetics was considered to be unnatural, and one when vaccination for smallpox (using material from cows) was so considered. Hardly anyone thinks that way now.

C. S. Lewis, for one, would have thought the idea unnatural -- see the opening quotation.

It might lead to ethical problems. Doudna points out that it might be possible for wealthy or powerful people to have germ cell alteration in the early embryos they have as their offspring, and thus to make class differences of power or money even more pronounced, by having more intelligent, talented, athletic, or disease-resistant descendants, because of genetic changes. (Intelligence is not easy to pinpoint, and is not simply inherited, and it's doubtful that we could modify an embryo to make it more intelligent, even if we badly wanted to, at present. Maybe never. But it's an example of something that might lead to class differentiation by inheritance, in addition to the class disparity problems that already exist.)

An ethical problem that Doudna doesn't consider a lot is the likelihood that human embryos will be produced, and discarded, which would be a serious ethical problem for many people. There are some embryos that are produced during in vitro fertilization that are not able to develop much past fertilization, and these might be used in experiments without cutting off the potential life of an embryo. But, of course, this begs the question of whether in vitro fertilization should be allowed.

There's the question of safety. By this, Doudna means that unforeseen consequences, changes in DNA that weren't planned, might be possible. It seems impossible to know about this possibility without engaging in extensive laboratory experiments.

So why should anyone want to do germ line alteration with CRISPR? It might, in fact has, produced crops and animals that are beneficial to us, cows with more muscle and less fat, for example. But the most important possibility is that an inherited disease might be eliminated, in some people, or in humans as a whole. An acquaintance of mine recently passed away because she had Huntington's disease, which is inherited. If the germ cells of people with this terrible condition could be modified, the disease could theoretically be eliminated, except for persons having it because of a new mutation. Doudna has spoken to people who are parents of children with genetic diseases, and they are much in favor of moving toward use of CRISPR to attack such conditions.

The Golden Rule of Matthew 7:12 says "Therefore whatever you desire for men to do to you, you shall also do to them; for this is the law and the prophets." This could be taken as guidance toward developing the technology, and using it to eliminate genetic diseases. However, on the other hand, it may be taken as guidance toward not doing anything that would harm a human embryo. See here for a discussion of abortion, in light of the Bible, a related topic.

The scientific community, with lots of input from others, has already considered the potential risks and benefits of altering genes, in bacteria and other organisms. One part of such consideration was the Asilomar Conference on recombinant DNA, in 1975. This led to a general consensus as to what kinds of work could be done, and what safety precautions should be used, and there have, to date, been no disasters because of recombinant DNA research.

I'm not aware of any conferences on human cloning, but the scientific community, at large, seems to have decided that such procedures simply shouldn't be done, and it is doubtful that they have been done. If they had, they would have led to an adult human with the same genes as some previous one.

Doudna and others, including some participants in the Asilomar Conference, met a couple of years ago, and collaborated on a document, "A prudent path forward for genomic engineering and germline gene modification," in April of 2015. This document has been published elsewhere, including here.

The following recommendations are given at the end of the article:

1. Strongly discourage, even in those countries with lax jurisdictions where it might be permitted, any attempts at germline genome modification for clinical application in humans, while societal, environmental, and ethical implications of such activity are discussed among scientific and governmental organizations. (In countries with a highly developed bioscience capacity, germline genome modification in humans is currently illegal or tightly regulated.) This will enable pathways to responsible uses of this technology, if any, to be identified.
2. Create forums in which experts from the scientific and bioethics communities can provide information and education about this new era of human biology, the issues accompanying the risks and rewards of using such powerful technology for a wide variety of applications including the potential to treat or cure human genetic disease, and the attendant ethical, social, and legal implications of genome modification.
3. Encourage and support transparent research to evaluate the efficacy and specificity of CRISPR-Cas9 genome engineering technology in human and nonhuman model systems relevant to its potential applications for germline gene therapy. Such research is essential to inform deliberations about what clinical applications, if any, might in the future be deemed permissible.
4. Convene a globally representative group of developers and users of genome engineering technology and experts in genetics, law, and bioethics, as well as members of the scientific community, the public, and relevant government agencies and interest groups—to further consider these important issues, and where appropriate, recommend policies.

National Public Radio and other sources report that the World Health Organization has appointed a group to establish "uniform guidelines for editing human DNA in ways that can be passed down to future generations." Doudna is not part of the group. That group seems to fulfill item 4 in the above list. (I checked the WHO web site on February 15, 2019, and was unable to find any reference to this group.)

How CRISPR works:
Vox has published an explanation of how CRISPR works, with graphics, and lists some of the things it might be used for.  Carl Zimmer, noted science writer, wrote another article on CRISPR, which, although a little older than the Vox article, is a fine introduction to how CRISPR was discovered, and how it works. This is the Wikipedia article, which is more technical than the others linked above.

Thanks for reading. We have responsibilities to other people, less fortunate than we are. Perhaps, in the near future, we may decide that those responsibilities are best carried out by somatic or germline DNA modification. May God help us.

Thanks for reading! 

Note: on February 20, 2019, I ran across an article that discusses most or all of the ethical issues involved in germline gene modification. It may be read here.