US: Human cloning - solely a medical issue?
A graduate of Emporia State University in Kansas, Zavos earned his PhD in reproductive physiology, biochemistry and statistics from the University of Minnesota. He has worked for more than 35 years in his infertility practice, research and academia, developing several new and innovative technologies in animal and human reproduction. He has authored or co-authored more than 400 peer-review publications.
UWN: Your clinics and companies provide gender selection for couples, with an 80% male selection and 75% female selection rate using a sperm selection process, and 100% using IVF/PGD. Are the numbers of patients using these procedures very large, and would you have concerns about this producing a population imbalance should the procedures become more commonplace? This would perhaps be a concern in societies that prefer one sex over another.
Zavos: Most countries prohibit performing a treatment procedure or the use of sperm or embryos with the purpose of producing, or attempting to produce, a child of particular sex, unless to avoid the risk of genetic transmission of sex-linked diseases. In the United Kingdom and in Europe in general, all licensed centres are forbidden from carrying out such procedures unless for medical reasons.
However, in the remaining territories and the US, centres can perform gender selection by sperm separation and artificial insemination using husband or partner sperm or by applying the PGD method (Preimplantation Genetic Diagnosis) where the embryos available after IVF (In Vitro Fertilisation) are selected based upon their gender (XX or XY) and transfered in utero for establishing a healthy pregnancy.
Now should people have concerns about these procedures producing a population imbalance? As European and US data show, the statistics available today refute concerns about national impacts on gender ratios in the developed world. Quite obviously, countries like India and China discriminate against female gender and therefore have seen significant changes in natural birth ratios.
But just because they do doesn't mean that we will see similar effects in the US and European countries. In other words, what is ethically acceptable in developed countries should not automatically apply to third-world countries, and vice versa. The people demand choices and people should be given choices for bettering their lives.
UWN: You have pioneered Round Spermatid Injection (ROSI) and Testicular Sperm Extraction (TSE) for harvesting immature sperm from males unable to provide mature sperm. Like the many other complex fertility techniques offered by your clinics, these are very expensive and chancy procedures. How do you respond to critics who claim that this is extravagant in an era when there are so many children awaiting adoption, etc.?
Zavos: Round spermatid injection is a method of Assisted Reproductive Technologies such as in Vitro Fertilisation or IVF in which precursors of mature sperm such as round or elongated spermatids are retrieved directly from the testes via tesicular biopsy or recovered from the ejaculate and used for the purposes of achieving ferilisation.
The process is very similar to the process of sperm injection but instead, immature sperm forms are used due to deficiencies in the man's testes to complete the phase of spermatogenesis and arrest themselves into an immature stage. This is originally developed by our team from here in the US in collaboration with our Japanese counterparts.
It is regarded as an experimental method due to the fact that not all is known about the activation of the spermatid and subsequent oocyte activation at the time of such injection. Our team is still experimenting and hoping to fully develop and implement this technique due to the fact that a large number of males are suffering from such meiotic arrests during spermatogenesis.
As to the criticism that such techniques are chancy and expensive for a couple to undertake, such criticism has no basis. Treating infertility is not an option for us but a responsibility. We all assume that if an infertile couple cannot have children and they can then notify their fertile neighbours to "make one for them" to adopt, this type of ideology can fly, but with such standards this world can not function.
Children that are put up for adoption should be adopted but they should not be the responsibility of the infertile couple to adopt, but rather their parents that brought them to this world in the first place.
UWN: You have not only offered cutting-edge assisted reproductive technologies to couples, but have also pressed forward in development of human reproductive cloning. In conjunction with colleagues in the Mediterranean Region, you indicate you have attempted implantations of over a dozen cloned human embryos for reproductive purposes. However, to date, none has resulted in a birth. What appear to be the physiological difficulties of achieving a human clone?
Zavos: Yes, we have created a number of cloned embryos utilising SCNT. The methodology for creating cloned embryos is not a secret, and it is 'easy to do' for those who know how to perform somatic cell nuclear transfers (SCNT) in mammalian cells and understand the basics in human embryology and embryo culture.
We have published the method that we used in creating human cloned embryos very successfully in refereed journals already. Anyone can visit our website at www.zavos.org and one can read one of the many publications on the methodology used to create the embryos, such as: Zavos, P & Illmensee, K: Possible treatment of male infertility by reproductive cloning: Technique for creating cloned human four-cell embryo and subsequent embryo transfer. Arch. Androl. 52:243-254, 2006.
Meanwile, the created embryos looked and behaved quite normally according to criteria that exist in the IVF industry today. We realise these embryos are not created via IVF but rather via SCNT and they grow in a normal manner and develope equally well. (See http://www.zavos.org/library/UAAN_A_150346.pdf to view the embryos.)
None of the women who received the embryos got pregnant and the most limiting factor was that we transferred embryos in women who were rather advanced in age; all of them were either perimenopausal or entered menopause years ago. They ranged in age from 37-52 years of age.
I must say at this time that our team is ready to do another group of patients but it will be necessary to involve women of sound reproductive potency to transfer the embryos this time in order to establish pregnancies. During the first phase, we cared about developing good embryos for transfer but now it is very important that we are developing good embryos for transfer and get pregnancies established.
We believe that getting a pregnancy and maintaining it in younger women will be possible. Our team has the expertise to guide a pregnancy successfully during the nine months of gestation.
UWN: In spite of the Bush administration attempts to get the UN to adopt a ban on human reproductive cloning, there is still no binding agreement to prevent it. What is your rationale for moving ahead with human reproductive cloning when there is pushback from a large proportion of the scientific and political community against it? What are some of the challenges?
Zavos: The challenges for carrying such research and studies in this field are quite numerous. For instance, within the United States, different religious, political, and academic organisations, as well as government advisory panels, have issued statements or recommendations regarding reproductive, therapeutic, and research cloning.
These entities have reached divergent conclusions on these issues - with some advocating a ban on all cloning activities and others arguing that cloning should be allowed for research purposes only. These divergent views in turn are based on different underlying values, including the view of the moral worth of a human embryo, conceptions of human personhood and human dignity, the importance of human individuality, the imperative to heal the sick, the right to reproductive autonomy, and the proper role of government in socially charged and ethically complex issues.
For this, I have testified before the US Congress twice and debated the issues on cloning all over the world before friendly and hostile audiences. For me, reproductive cloning is here and it is here to stay! As of today, there is no law that prevents anyone in carrying cloning procedures in the US and Bush and company have failed (it seems that Bush and failure seem to be synonyms) in initiating any leadership in this area that can be of any significance.
Unfortunately, other countries have taken advantage of the inability of the American leaders to take any initiative and are developing the technology and patenting it. Americans will be paying the Swiss, Chinese, Israelis and others in utilising their patents in applying those types of procedures in the future because our leadership has failed us. What a shame!
UWN: The Korean researcher who first claimed to clone a human embryo was found to have fabricated the data. Does that make your team the first to conduct human cloning?
Zavos: I know the Korean team and I truly think that they are very capable in doing and performing SCNT in humans and doing serious work. However, like in all aspects of any 'hot' scientific work they met destruction when they entered areas that they did not belong and decided to 'cut corners' in doing serious scientific work.
This could happen to any of us but what I always believed in all of our scientific efforts over the last 35 years, one should never attempt to mislead the scientific world and the public for the sake of trying to score points. Our team remained focused and we paid the price with our failures and successes.
That's the price that one pays when one does 'cutting edge' research. We are the undisputed first to create human cloned embryos for reproductive purposes and transfer them to women for the purpose of achieving a pregnancy. What's left for us is to achieve such pregnancy. We are not too far off from doing that.
UWN: Reproductive procedures that many hesitate to use with humans are commonplace in animal breeding. Can you briefly elaborate on the importance of animal research and its role in your reproductive biology work?
Zavos: As a well trained biologist and being very familiar with animal research, I have tried to model all of my human research utilising animal models. In our efforts to study SCNT and how the DNA reprogramming takes place and all the details about the activation process is initiated in a post SCNT oocyte, we decided to employ animal models that can give us the answers.
We have developed a 'one of a kind' animal model utilising the human genome and bovine eggs. This model was proven to be a milestone for this type of research and was able to assist us in improving our results when SCNT was attempted with human eggs. We were accused that we were trying to create 'half human and half bovine' entities, which is material for stand-up comedy, but today our work is duplicated by the very people that criticised us.
Cloning in humans today is a very fast developing process and I can see the date that a large number of commercially raised cattle and other animal models will be produced via SCNT. The best genetic lines for meat or milk or other commodities will be perpetuated and the advantages for such process are tremendous, and the sky is the limit.
UWN: There was a debate about the overall health of cloned animals, mostly about longevity, tissue aging and cancer formation. What are the possible health complications that cloned humans might risk facing? Will they have an increased risk of tissue aging or cancer?
Zavos: During the early debates on cloning, the opponents tried to mislead the public that all those things are happening routinely to all clones. The current results and experimentation prove that it is not the case and this is because the early cloners were not as sophisticated as those of today's market. What was happening was that if it is not done correctly, it can result in problems which are true in all aspects of science.
Today, results yield perfectly normal animals that live normal lives without complications. In my view, three criteria would need to be fulfilled before the safety of human reproductive cloning could be established: (1) improved animal cloning procedures together with reduction in observed abnormalities, or a demonstration that humans would be different with regard to these defects; (2) a demonstration that cloned embryos are normal with respect to imprinting and reprogramming; and (3) the development of methods to monitor cloned embryos and foetuses for cloning related defects via PGD and other genetic screening technologies.
Those criteria are met and further research will make cloning even safer. I tend to believe that normal cloned babies can be produced under the current knowledge and it is a matter of time that such an event would take place.
UWN: In what way do you perceive human cloning might or will change future human life?
Zavos: According to many opponents to human cloning, human reproductive cloning would, for the first time, allow offspring to be produced using the genetic contribution of only one individual. For some, this shift from two genetic contributors to one would be a radical and unwelcome departure from the natural procreative process, one that would 'usurp the authority of God'.
Some argue that reproductive cloning 'does not meet Biblical standards for procreation' in which children are begotten not made. The Koran does not preach the same and therefore there are differences in interpreting cloning among different religions. I personally believe this is not a religious, political or moral issue, but rather a medical issue that should stay between the patients and their doctors.
Furthermore, in its resolution on cloning, the American Bar Association's House of Delegates also recognised the possibility that reproductive cloning may have occurred or would occur in the near future.
Thus, the House of Delegates expressed its support for national law or policy that would establish a "presumption that a live birth resulting from reproductive cloning is a human being" and "guarantee that any such human being is a person, legally separate and distinct from its biological progenitor, with all rights accorded to any other live born human being under existing law."
I had the privilege of addressing the American Bar Association's House of Delegates in the past and I believe that I was able to convince them that "any born human being is a person under the law".
* John Richard Schrock is a professor of biology and director of biology education at Emporia State University in Kansas.