Dolly the sheep clones age healthily

The sheep were found to be as healthy as naturally conceived animals.

A study published today in Nature reviews the health of the four clones of infamous Dolly the sheep, the world’s first cloned animal which was born 20 years ago. Concerns were raised when Dolly died at the comparatively young age of 6.5 years old, however her clones have now all reached a robust nine years old without major health problems. The study’s lead author, Kevin Sinclair, told us more.

ResearchGate: Why did you want to check on the health of Dolly’s clones and what did you find??

Kevin Sinclair:  Concerns regarding premature ageing and the health status of cloned offspring have been around since the birth of Dolly. In this study, we undertook comprehensive health assessments of aged cloned sheep, including four clones (identical sisters) of Dolly, and found these animals to be as healthy as normal aged sheep. We chose to assess three common age-related problems – that is, those associated with metabolic disorders and obesity, high blood pressure and arthritis. We found our animals to be healthy in all three regards, with no evidence of premature ageing. Our study demonstrates that a subset of cloned embryos are capable of undergoing successful reprogramming and implantation in the uterus following transfer to surrogates. These embryos give rise to viable offspring that age normally.

RG: In what ways did the cloning of Dolly the sheep and the subsequent four clones progress the field of science?

Sinclair: Dolly’s main legacy is that she demonstrated for the first time that it is possible to reprogram a fully differentiated animal cell – often referred to as a somatic cell or adult cell belonging to the body – to a pluripotent cell – that is one that is capable of developing into the many different cell types within the body. This inspired other scientists to develop laboratory methods for generating pluripotent stem cells – often referred to as induced pluripotent stem cells or iPS cells. These cells offer great potential for therapeutic use in regenerative medicine, screening new medicines and drugs, and research into early development. Our studies provide compelling evidence that we can expect some of these reprogrammed cells to be perfectly normal. Where there is some then there can be many – and the goal is to increase the proportion of fully reprogrammed pluripotent cells and cloned embryos in the future.

RG: What are the next steps in this research?

Sinclair: Our animals are at an advanced stage in their lives now – one year older than reported in the paper –  so that in the not too distant future we must consider a humane experimental endpoint. This is so that we can undertake a full histopathological analyses of different organs and tissues. We are also looking to isolate enriched populations of cells from different tissues to undertake whole genome epigenetic analyses, and to study aspects of mitochondrial and telomere biology.

Professor Sinclair with the four Dolly clones

RG: Is cloning and the research surrounding it still viewed with high levels of stigma, as it was 20 years ago when Dolly was cloned?

Sinclair: Judging from the media interest surrounding the 20th anniversary of the birth of Dolly I would say no. Many of the fears raised back in the late 1990s regarding cloning have disappeared, and people are becoming increasingly reassured that these technologies can be a force for good and not evil. The fact that we have demonstrated that cloned offspring can live long and healthy lives will hopefully reinforce these views.

RG: Since the birth of Dolly’s clones, how common has cloning animals become?

Sinclair: I believe that there have now been 23 species cloned – some quite routinely – including cattle in North America and companion animals in Korea. However, this area is still under-researched and underdeveloped in several countries, hence cloning is not as common as it could be.

RG: For what purposes are animals cloned today?

Sinclair: Today, animals are cloned predominately for research to further develop and refine procedures and assess animal health and welfare. As for non-research applications, cloning is especially useful for animal breeding and increasing the influence of valuable females in particular.

RG: Are cloned animals generally as healthy as naturally conceived animals?

Sinclair: Our detailed study and less detailed studies by others suggest that once cloned animals get past the first month or two of life they are healthy. However, early pregnancy loss and neonatal losses are still greater with cloning than natural conception or assisted reproduction (IVF). Current research endeavors are attempting to overcome this problem.

Image credit: Nottingham University