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City Weekend

His DNA test for Down’s Syndrome benefited millions but raised ethical dilemma about designer babies. Now Dr Dennis Lo predicts Hong Kong is ready for biotech boom

In a three-part series, the Post talks to winners of the InnoStars Awards, organised by Our Hong Kong Foundation to recognise leaders and promote innovation. In the first part, we sit down with Dr Dennis Lo, a pioneer in DNA testing

PUBLISHED : Saturday, 28 April, 2018, 4:02pm
UPDATED : Saturday, 28 April, 2018, 4:02pm

Dennis Lo Yuk-ming, 54, is one of Hong Kong’s foremost innovators in the realm of medical science. He was educated at Oxford University, the director of the Li Ka-shing Institute of Health Sciences and professor of medicine at Chinese University. He made a breakthrough discovery in DNA testing of pregnant women 30 years ago that led to the development of non-invasive testing for Down’s syndrome in the fetus. His discovery has benefited millions of women each year but raised an ethical dilemma about designer babies and DNA tests in our everyday lives. Lo, a winner of the Future Science Prize, considered the Chinese equivalent of the Nobel Prize, says the conditions are ripe for a biotech boom in the city.

What was your discovery about?

I was a PhD student in Oxford University and I had this idea around October 1996. Even before I was a medical student in Britain, I was thinking there might be some baby cells in the mother’s blood. So I was actually working on that from 1989 through 1997. In 1989, we found the number of fetal cells was very low. So it was difficult to do a reliable test.

In September 1996, I saw a couple of papers in a journal which said cancer cells would release DNA into the plasma of a patient. I realised a cancer growing in a patient was similar to a baby growing in the mother.

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So I thought I could do something to look for fetal DNA in the mother’s plasma. I was about to move from Britain to Hong Kong and I didn’t have a lot of grants to do tests. So I could only do something cheap, but I had no idea how to get this DNA from plasma. I thought what if I cook it, just like cooking some noodles? I took a little bit of plasma and heated it for five minutes, and took a little of that juice to be tested. Strangely, even with that crude mixture, I was able to see a few DNA signals. For eight years, I had been looking at the wrong part of blood because I had thrown away that good bit, the plasma. I only looked at the cells.

What happened when you returned to Hong Kong?

I returned to Hong Kong in January 1997. That July, I published a paper reporting for the first time the presence of cell-free fetal DNA in the blood plasma of a pregnant woman. It meant we had a new way to test the genetic well-being of the baby just by looking at the blood of the mother.

The next question is how much of that stuff (in plasma) is fetus. At that time I had to use a new technology to measure the concentration. But that technology was very new and there was no machine available in Hong Kong. I remember, I had to persuade my first boss here at Chinese University – Magnus Hjelm, a Swedish scientist who used to work in London but after retirement came to CUHK to head the department of chemical pathology – during a Christmas party to buy that machine for me, and it cost close to HK$1 million (US$127,000). Within five minutes he said yes … so then when we measured the plasma we found that close to 10 per cent of DNA in the mother’s plasma is from the baby. It was also the first time. That was published in 1998.

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What did you do with your findings?

We decided to use it diagnostically. So we can use it to determine the gender of the baby. It is useful because some genetic diseases would preferentially affect boys, like haemophilia.

Another is for blood group test. If the mother is rhesus negative and the baby is positive, then the mother can produce antibodies to attack the baby. It’s called rhesus haemolytic disease.

Those two applications turned out to be very accurate, sexing and the blood group and those were then introduced into clinical practice.

How long did it take you to develop the DNA prenatal test for Down’s syndrome?

We decided to be more ambitious, but it took us over 10 years to do to apply our findings to and that’s for Down’s syndrome, from 1997 to 2008. The reason why it’s so difficult is because Down’s syndrome is a chromosome disorder. A normal cell will have 23 pairs of chromosomes, or 46 chromosomes. A Down’s syndrome baby has 47. Somehow you have to count how many chromosomes the baby has and this is difficult because normally you have a cell and you see how many chromosomes are there inside. But for our field there is no cell – the DNA is swimming outside the cell. How can you measure that? It took us 11 years to figure it out. In 2008, we published in The Lancet and then it took the next three years to do clinical trials. The DNA test turned out to be 99.8 per cent accurate for Down’s syndrome.

Is it the case that amniocentesis – a procedure in which amniotic fluid is sampled using a needle inserted into the uterus to screen for fetal abnormalities – is no longer the gold standard for Down’s syndrome diagnosis?

As a result of our test, the number of amniocentesis done is greatly reduced, easily halved in dozens of countries which use our technology. For example in China, every year there are 18 million pregnancies and 4 million of those actually use the test. Overall one in 700 babies would have Down’s syndrome.

After 2011, there were other chromosomes added to the test. In some of the high-end products around the world, you can easily test for 15 or 20 chromosomal abnormalities.

What advice can you give young people who want to set up biotechnology start-ups?

Now is a very good time. I have been in Hong Kong for 20 years and I have never seen the atmosphere for start-ups, and the resources for start-ups, as intense as now. When I first started 20 years ago, no one had start-ups and it was very difficult to get money. Investors at that time knew the business side, but they didn’t know the science side. Also, it was very difficult to get a CEO who knew both. But in the past few years I have noticed a sea change in atmosphere.

Has the human genome sequencing spurred the biotech revolution?

When I first started, there was no human genome sequence. Now, we’ve got that and some of the sequences were unimaginable in those days. The first human genome sequence was produced after 13 years of work. Now I have a machine which can sequence you 30 times in two days at much less cost.

The first human genome was sequenced at a cost of US$3 billion. But now I can sequence your genome, with the cheapest way at US$1,000 or about HK$10,000.

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How about the moral implications of creating designer babies?

The reason we developed this technology is to save the baby from being unnecessarily harmed by conventional method. Because conventionally, if you test for those chromosomes accurately you have to stick a needle in the womb in a process called amniocentesis. Every time you do that there is a 0.5 per cent chance that you may harm the baby. Then you talk about the eugenics side of things. The question was: what do you use this technology to test for? So far all those things were testing for serious genetic or chromosome diseases. Your eugenics problem might arise if people use it to test characteristics rather than diseases.

So theoretically, it might come to a point that there won’t be any more Down’s syndrome babies?

When we use the technology we counsel the women so they know what the test is about and what they would do with the result. Across the world, some women take the test so they could prepare. Even if they know the baby is affected, they may not necessarily terminate. At the end of the day it is a woman’s choice.

Do you have any religion?

I don’t.

So all this is more of scientific interest for you?

No, I think we want to develop something that can help.

How did this DNA test for Down’s syndrome come into the market?

The odd thing is when I first started, we actually had 1,000 patents on that. Initially, the university licensed it to a British company. But that company didn’t realise that this was valuable so they sat on the technology for three years and after that they said it was rubbish. So they gave it back to the university. Obviously they made a big mistake. In early 2002, in a meeting in Pattaya, Thailand, I met Charles Cantor, the chief scientific officer for a San Diego-based US company called Sequenom and asked him to come to my talk, and he came. He immediately thought this technology has potential. We actually started to work together and in 2005, Sequenom licensed our technology and after that we worked together and the product was launched at the end of 2011.

After that, Sequenom and a company called Illumina, decided to pool their resources. We (CUHK) licensed our technology to these two companies and they then sub-licensed the technology to 40 other companies. So in the whole world there may be 100-odd companies that make tests like this.

THE QUIRKY SIDE OF DR DENNIS LO

Do you have a hero?

I’ve always been very interested in science. In the era of DNA, I was inspired by (American biologist James) Watson and (English physicist Francis) Crick. I have a car whose registration number is DNA1. Actually, the reason why I got that number apart from DNA is because my name is Dennis and my wife’s name is Alice. I wanted to get DNA but someone else got it so the next thing was DNA1. Nobody wanted it. I guess they don’t care about DNA in Hong Kong.

Any favourite places for travel?

I like to travel a lot, this is one of the privileges of a scientist because you go to a lot of conferences.

For my favourite places to visit, I would say Iceland and Italy. I have been to Italy approximately eight times. I like the history, weather, food and friendliness of the people.

My wife Alice and I sometimes travel for leisure. I also like photography. So we went to Iceland to take pictures and things, see the Northern Lights. I would say South Africa is among my favourite places to visit. Cape Town, in particular, is lovely. I like the drive from Cape Town to the Cape of Good Hope.

Do you have other hobbies?

I like movies as you are sucked into a different world. Actually you might have read one of the ideas that I had about sequencing the whole genome of the baby was from watching a Harry Potter movie. At that time we were trying to crack the fetal genome.

Any plans to write a book?

I haven’t written books – yet. Maybe when I retire, when I have more time.

What do you do to relax?

My mother used to be a music teacher at school. I learned how to play the piano but my brother is more accomplished. I like to listen to music to relax.